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Cell therapy with adipose tissue-derived human stem cells in the urinary bladder improves detrusor contractility and reduces voiding residue

A terapia celular com células-tronco humanas derivadas do tecido adiposo na bexiga urinária melhora a contratilidade do detrusor e reduz o resíduo miccional

Abstract

Detrusor hypocontractility (DH) is a disease without a gold standard treatment in traditional medicine. Therefore, there is a need to develop innovative therapies. The present report presents the case of a patient with DH who was transplanted with 2 x 106 adipose tissue-derived mesenchymal stem cells twice and achieved significant improvements in their quality of life. The results showed that cell therapy reduced the voiding residue from 1,800 mL to 800 mL, the maximum cystometric capacity from 800 to 550 mL, and bladder compliance from 77 to 36.6 mL/cmH2O. Cell therapy also increased the maximum flow from 3 to 11 mL/s, the detrusor pressure from 08 to 35 cmH2O, the urine volume from 267 to 524 mL and the bladder contractility index (BCI) value from 23 to 90. The International Continence on Incontinence Questionnaire - Short Form score decreased from 17 to 8. Given the above, it is inferred that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative and efficient therapeutic strategy for DH treatment and improves the quality of life of patients affected by this disease.

Keywords:
adipose derived mesenchymal stem cells; cellular therapy; urinary bladder; urodynamics; lower urinary tract

Resumo

A Hipocontratilidade Detrusora (HD) é uma doença sem um tratamento padrão-ouro na medicina tradicional. Logo, há a necessidade de desenvolvimento de terapias inovadoras. O presente relato apresenta um caso de paciente com HD transplantado duas vezes com 2 x 106 células-tronco mesenquimais derivadas do tecido adiposo que obteve melhoras significativas em sua qualidade de vida. Os resultados demonstraram que a terapia celular reduziu o resíduo miccional de 1.800mL para 800mL; a Capacidade Cistométrica Máxima de 800 para 550mL; a complacência de 77 para 36,6mL/cmH2O. A terapia celular também aumentou o fluxo máximo de 3 para 11mL/s; a pressão detrusora de 08 para 35cmH2O; o volume urinado de 267 para 524mL e o índice de contratilidade vesical (BCI) de 23 para 90. O score do International Continence on Incontinence Questionare - Short Form passou de 17 para 8. Diante do exposto, infere-se que o transplante de células-tronco mesenquimais derivadas do tecido adiposo é uma estratégia terapêutica inovadora e eficiente para o tratamento da HD e para melhoria da qualidade de vida de pacientes acometidos por essa doença.

Palavras-chave:
células-tronco mesenquimais derivadas de tecido adiposo; terapia celular; bexiga urinária; urodinâmica; trato urinário inferior

1. Introduction

Detrusor hypocontractility (DH) is related to short-duration contraction of the detrusor, which results in low pressure associated with low urinary flow (D’ancona et al., 2019D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897. PMid:30681183.
http://dx.doi.org/10.1002/nau.23897...
). Patients affected by this disease experience a slow urinary flow, hesitation and an increased effort to urinate, a feeling of incomplete bladder emptying and high postvoiding residue (Gammie et al., 2016GAMMIE, A., KAPER, M., DORREPAAL, C., KOS, T. and ABRAMS, P., 2016. Signs and symptoms of detrusor underactivity: an analysis of clinical presentation and urodynamic tests from a large group of patients undergoing pressure flow studies. European Urology, vol. 69, no. 2, pp. 361-369. http://dx.doi.org/10.1016/j.eururo.2015.08.014. PMid: 26318706.
http://dx.doi.org/10.1016/j.eururo.2015....
).

According to Levanovich et al. (2015)LEVANOVICH, P.E., DIOKNO, A., HASENAU, D.L., LAJINESS, M., PRUCHNIC, R. and CHANCELLOR, M.B., 2015. Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. International Urology and Nephrology, vol. 47, no. 3, pp. 465-467. http://dx.doi.org/10.1007/s11255-015-0924-1. PMid:25663053.
http://dx.doi.org/10.1007/s11255-015-092...
, muscle-derived cells are able to reduce cystometric capacity and restore the ability to urinate in small volumes. Even with these improvements, patients with DH remain dependent on catheterization. This was the only cell therapy report found in the researched literature for the treatment of DH. However, there are studies in urology with cell therapy and tissue engineering for the repair of renal, gonadal, urethral sphincter and bladder tissues (Becker and Jakse, 2007BECKER, C. and JAKSE, G., 2007. Stem cells for regeneration of urological structures. European Urology, vol. 51, no. 5, pp. 1217-1228. http://dx.doi.org/10.1016/j.eururo.2007.01.029. PMid:17254699.
http://dx.doi.org/10.1016/j.eururo.2007....
; Levanovich et al., 2015LEVANOVICH, P.E., DIOKNO, A., HASENAU, D.L., LAJINESS, M., PRUCHNIC, R. and CHANCELLOR, M.B., 2015. Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. International Urology and Nephrology, vol. 47, no. 3, pp. 465-467. http://dx.doi.org/10.1007/s11255-015-0924-1. PMid:25663053.
http://dx.doi.org/10.1007/s11255-015-092...
; Assis et al., 2019ASSIS, P.V., NEVES, S.C., TAKITA, L.C., TURA, B.B., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2019. Cell therapy with mesenquimial stem cells of bone marrow improves renal function in pre-clinical module. International Journal of Developmental Research, vol. 09, no. 3, pp. 26613-26619.; Oliveira et al., 2019OLIVEIRA, J.R., NEVES, S.C., REZENDE, G.C.D., MIIJI, L.N.O., PELIZARO, B.I., OLIVEIRA, D.D.M., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2019. Cell therapy with adipose tissue mesenchymal stem cells improves the quality of the germinal epithelium in swiss mice. International Journal of Developmental Research, vol. 09, no. 3, pp. 26280-26288.). These facts demonstrate the need to continue studies in this area.

The fact that conventional therapies do not present the desired gold standard reinforces the need for studies of DH treatment. Given the above, in the present study, the effects of cell therapy with adipose tissue-derived human mesenchymal stem cells in the treatment of DH are reported.

2. Case History

A 74-year-old white male patient with a history of a weak and intermittent urinary stream, very prolonged urination, hesitation, a feeling of incomplete emptying, pain and bulging in the hypogastrium was referred to the Urology Service of Hospital Universitário Maria Aparecida Pedrossian (HUMAP), a public hospital of Sistema Único de Saúde (SUS), Campo Grande, MS, Brazil. The previous history showed recurrent urinary infection and the use of a Foley urinary catheter due to urinary retention for one year. The patient had no history of smoking, alcoholism and comorbidities except hypertension. The patient was taking losartan (50 mg/day).

On physical examination, he had normal external genitalia, a bulging abdomen and pain in the hypogastric region. Digital rectal examination revealed a prostate < 30 grams, nodules and painlessness. Blood count and coagulogram results were normal. Ultrasonography showed normal kidneys, a bladder with an accentuated voiding residue and a 20-gram prostate.

Urethrocystoscopy showed a normal penile, bulbar and membranous urethra; a normal prostatic urethra; an open bladder neck; a topical ureteral meatus; and smooth bladder walls without trabeculations.

3. Results

The patient underwent a urodynamic study to assess voiding dysfunction. The initial uroflowmetry test did not trigger urination and showed a voiding residue of 1,800 mL measured by urinary catheter. Differential cystometry showed a maximum cystometric capacity (MCC) of 800 mL, a bladder compliance of 77 mL/cmH2O, decreased sensitivity, losses with effort manoeuvres and the absence of contractions. The flow-pressure study presented a maximum flow (Qmax) of 3 mL/s, a detrusor pressure at maximum flow (pdetqmax) of 8 cmH2O, a urine volume of 267 mL, and a detrusor contractility index (bladder contractility index: BCI = pdetqmax + 5 x Qmax) of 23. The values obtained with this urodynamic study were compatible with DH (Table 1).

Table 1
Absolute values and percentage of variation in the results of uroflowmetry, cystometry and flow pressure study and score of the International Continence on Incontinence Questionare - Short From, before and after cell therapy.

The ICIQ-SF (International Continence on Incontinence Questionnaire - Short Form) was applied to assess quality of life, with the patient obtaining a score of 17 (Table 1).

The standard treatment for cases of DH was started with clean intermittent catheterization and clinical and laboratory follow-up. The maximum volume in each drain was 400 mL. In the present condition, the patient needed 5 catheters/day. Given the above, the patient was recruited for treatment with mesenchymal stem cells (Opinion confirmed by CEP/CONEP number #2,745746).

After agreement and signing the informed consent form, the patient underwent liposuction for peripheral fat collection from the inner face of the right and left thigh. The procedure was performed by a specialist in plastic surgery on an outpatient basis. A total of 125 mL of anaesthetic solution containing 20% lidocaine without adrenaline, 0.9% saline and 8.4% sodium bicarbonate was used. A total of 200 ml of phosphate buffer solution (PBS) was removed. Then, the material was sent to the Center for Studies in Stem Cells, Cell Therapy and Toxicological Genetics (CeTroGen) and processed according to a current standard operating procedure established by Pesarini et al. (2018)PESARINI, J.R., OLIVEIRA, E.J.T., PESSATTO, L.R., RABACOW, A.P.M., CAMASSOLA, M., DOS SANTOS, B.P., DE BARROS, M.E., CANTERO, W.B., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2018. Calcitriol combined with calcium chloride causes apoptosis in undifferentiated adipose tissue-derived human mesenchymal stem cells, but this effect decreases during adipogenic differentiation. Biomedicine and Pharmacotherapy, vol. 108, pp. 914-924. http://dx.doi.org/10.1016/j.biopha.2018.09.083. PMid:30372903.
http://dx.doi.org/10.1016/j.biopha.2018....
.

At 60 days, the patient underwent outpatient urethrocystoscopy for transplantation of 2 x 106 adipose tissue-derived mesenchymal stem cells. The transplant was performed at 5 points in the body of the bladder above the vesical triangle. A second transplant was performed 30 days after the first following the same principles.

The patient was clinically followed up during and after the transplant and submitted to a cultured urine test. The patient did not present any complications, and the exams showed normal results.

At 60 days after transplantation, the patient underwent a new urodynamic study. The initial uroflowmetry test showed a maximum flow of 10 mL/s, an average flow of 5 mL/s, a urine volume of 176 mL and a residual volume of 800 mL. Differential cystometry showed a maximum cystometric capacity of 550 mL, a bladder compliance of 36.6 mL/cmH2O, decreased sensitivity with no loss and involuntary detrusor contraction. The pressure-flow study showed a maximum flow of 11 mL/s and pdetQmax of 35 cmH2O. The urine volume was 524 mL, and the BCI value reached 90 (Table 1).

When administered the ICIQ-SF, the patient received a score of 8 (Table 1).

4. Discussion

The patient was unable to trigger urination. Therefore, the only way to empty the bladder was through clean intermittent catheterization. In the first uroflowmetry test, the patient had a voiding residue of 1800 mL. This volume suggests a diagnosis of detrusor contractility. Detrusor contractility is diagnosed for patients with voiding residues greater than 1,000 mL (Anderson and Grant, 1991ANDERSON, J.B. and GRANT, J.B., 1991. Postoperative retention of urine: a prospective urodynamic study. BMJ (Clinical Research Ed.), vol. 302, no. 6781, pp. 894-896. http://dx.doi.org/10.1136/bmj.302.6781.894. PMid:1709058.
http://dx.doi.org/10.1136/bmj.302.6781.8...
). However, it was observed that this patient had a detrusor pressure of 8 cm/H2O. Therefore, the suggested diagnosis was DH.

The diagnosis of DH was confirmed (I) by the low maximum flow of only 3 mL/s, while the expected one was above 15 mL/s (Reynard et al., 1998REYNARD, J.M., YANG, Q., DONOVAN, J.L., PETERS, T.J., SCHAFER, W., DE LA ROSETTE, J.J., DABHOIWALA, N.F., OSAWA, D., LIM, A.T. and ABRAMS, P., 1998. The ICS-‘BPH’Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. British Journal of Urology, vol. 82, no. 5, pp. 619-623. http://dx.doi.org/10.1046/j.1464-410X.1998.00813.x. PMid:9839573.
http://dx.doi.org/10.1046/j.1464-410X.19...
); (II) due to the small detrusor pressure, which was only 8 cmH2O, while the expected one was 30 cmH2O (Zerati et al., 2010ZERATI, F.M., NARDOZZA, J.A. and REIS, R.B., 2010. Urologia fundamental. São Paulo: Planmark. 274 p.); and (III) because of the low BCI value, which was only 23, while the expected range was between 100 and 150 (D’ancona et al., 2019D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897. PMid:30681183.
http://dx.doi.org/10.1002/nau.23897...
).

This condition interfered with the quality of life of the patient, who obtained a score of 17 on the ICIQ-SF, which has a maximum score of 21 (Tamanini et al., 2004TAMANINI, J.T., DAMBROS, M., D’ANCONA, C.A., PALMA, P.C. and RODRIGUES NETTO JUNIOR, N., 2004. Validação para o português do “International Consultation on Incontinence Questionnaire -- Short Form” (ICIQ-SF). Revista de Saude Publica, vol. 38, no. 3, pp. 438-444. http://dx.doi.org/10.1590/S0034-89102004000300015. PMid:15243675.
http://dx.doi.org/10.1590/S0034-89102004...
). Patients with DH reduce or withdraw from their daily activities, especially from social interactions, as clean intermittent catheterization is difficult to perform outside the home. In addition, this disease leads to urine loss, which is perceived by the unpleasant smell and causes social embarrassment (Teunissen et al., 2006TEUNISSEN, D., VAN DEN BOSCH, W., VAN WEEL, C. and LAGRO-JANSSEN, T., 2006. “It can always happen”: the impact of urinary incontinence on elderly men and women. Scandinavian Journal of Primary Health Care, vol. 24, no. 3, pp. 166-173. http://dx.doi.org/10.1080/02813430600739371. PMid:16923626.
http://dx.doi.org/10.1080/02813430600739...
).

Given the above, it is believed that conventional therapy, which involves clean intermittent catheterization and the surveillance of renal function and urinary tract infections (Bayrak and Dmochowski, 2019BAYRAK, Ö. and DMOCHOWSKI, R.R., 2019. Underactive bladder: a review of the current treatment concepts. Turkish Journal of Urology, vol. 45, no. 6, pp. 401-409. http://dx.doi.org/10.5152/tud.2019.37659. PMid:30817271.
http://dx.doi.org/10.5152/tud.2019.37659...
), leads to improvements for these patients. However, the results are not satisfactory. Therefore, there is a need for innovative therapies that can improve the quality of life of patients with results beyond those obtained with conservative treatments. In this context, cell therapies using mesenchymal stem cells stand out.

In the present study, two transplants with adipose tissue-derived mesenchymal stem cells were able to confer the ability to trigger urination. In addition, the uroflowmetry test showed an improvement of 1000%, 500% and 17600% in maximum flow, mean flow and urine volume, respectively. The improvement of these parameters resulted in a 56% lower voiding residue. It was also observed that the CCM reached a value of 550 mL, and the expected value was between 350 and 500 mL, which demonstrated a reduction of 31%. Initially, the patient had urinary loss, and after therapy, the cells stopped. Bladder compliance showed a reduction of 52%, decreasing from 77 mL/cmH2O to 36.6 mL/cmH2O, with the expected values being above 30 mL/cmH2O (D’ancona et al., 2019D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897. PMid:30681183.
http://dx.doi.org/10.1002/nau.23897...
).

The pressure flow study demonstrated a maximum flow increase of 267%. This parameter increased from 3 to 11 mL/s, and the expected range was above 15 mL/s (Ahmed et al., 2016AHMED, A., FARHAN, B., VERNEZ, S. and GHONIEM, G.M., 2016. The challenges in the diagnosis of detrusor underactivity in clinical practice: a mini-review. Arab Journal of Urology, vol. 14, no. 3, pp. 223-227. http://dx.doi.org/10.1016/j.aju.2016.06.005. PMid:27547465.
http://dx.doi.org/10.1016/j.aju.2016.06....
). The urine volume increased by 96%. However, the voiding residue remains high according to D’Ancona et al. (2019)D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897. PMid:30681183.
http://dx.doi.org/10.1002/nau.23897...
, who report this should be up to 50 mL. The BCI value showed an increase of 291%, reaching a value of 90, with the expected value being between 100 and 150 (D’ancona et al., 2019D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897. PMid:30681183.
http://dx.doi.org/10.1002/nau.23897...
).

All these improvements were directly reflected in the quality of life of the patient who presented an ICIQ-SF score of 8 after cell therapy. Thus, there was a 53% reduction in the score, which directly reflected the patient's daily life and the resumption of their daily activities and social interaction. It is also noteworthy that this patient’s intermittent catheterizations decreased from 5 to 2 per day, and he acquired spontaneous urination. Given the above, we infer that the transplantation of adipose tissue-derived mesenchymal stem cells is an innovative therapeutic strategy for the treatment of DH and for improving the quality of life of patients affected by this disease.

Mesenchymal stem cells, especially those derived from adipose tissue, have been successfully used clinically (Bacakova et al., 2018BACAKOVA, L., ZARUBOVA, J., TRAVNICKOVA, M., MUSILKOVA, J., PAJOROVA, J., SLEPICKA, P., KASALKOVA, N.S., SVORCIK, V., KOLSKA, Z., MOTARJEMI, H. and MOLITOR, M., 2018. Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review. Biotechnology Advances, vol. 36, no. 4, pp. 1111-1126. http://dx.doi.org/10.1016/j.biotechadv.2018.03.011. PMid:29563048.
http://dx.doi.org/10.1016/j.biotechadv.2...
). Their applications in skin rejuvenation and wound healing (Hanson et al., 2010HANSON, S.E., GUTOWSKI, K.A. and HEMATTI, P., 2010. Clinical applications of mesenchymal stem cells in soft tissue augmentation. Aesthetic Surgery Journal, vol. 30, no. 6, pp. 838-842. http://dx.doi.org/10.1177/1090820X10386364. PMid:21131458.
http://dx.doi.org/10.1177/1090820X103863...
; Tobita et al., 2011TOBITA, M., ORBAY, H. and MIZUNO, H., 2011. Adipose-derived stem cells: current findings and future perspectives. Discovery Medicine, vol. 11, no. 57, pp. 160-170. PMid:21356171.; Nae et al., 2013NAE, S., BORDEIANU, I., STĂNCIOIU, A.T. and ANTOHI, N., 2013. Human adipose-derived stem cells: definition, isolation, tissue-engineering applications. Romanian Journal of Morphology and Embryology, vol. 54, no. 4, pp. 919-924. PMid:24398986.; Kokai et al., 2014KOKAI, L.E., MARRA, K. and RUBIN, J.P., 2014. Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Translational Research; the Journal of Laboratory and Clinical Medicine, vol. 163, no. 4, pp. 399-408. http://dx.doi.org/10.1016/j.trsl.2013.11.009. PMid:24361334.
http://dx.doi.org/10.1016/j.trsl.2013.11...
), in Parry-Romberg syndrome treatment (Sterodimas et al., 2010STERODIMAS, A., DE FARIA, J., NICARETTA, B. and PITANGUY, I., 2010. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. Journal of Plastic, Reconstructive & Aesthetic Surgery; JPRAS, vol. 63, no. 11, pp. 1886-1892. http://dx.doi.org/10.1016/j.bjps.2009.10.028. PMid:19969517.
http://dx.doi.org/10.1016/j.bjps.2009.10...
), inflammatory and/or autoimmune disorders such as Graft versus host disease, multiple sclerosis and Crohn's disease (Locke et al., 2009LOCKE, M., WINDSOR, J. and DUNBAR, P.R., 2009. Human adipose-derived stem cells: isolation, characterization and applications in surgery. ANZ Journal of Surgery, vol. 79, no. 4, pp. 235-244. http://dx.doi.org/10.1111/j.1445-2197.2009.04852.x. PMid:19432707.
http://dx.doi.org/10.1111/j.1445-2197.20...
; Frolich et al., 2014FRÖLICH, K., HAGEN, R. and KLEINSASSER, N., 2014. Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in otorhinolaryngology. Laryngo- Rhino- Otologie, vol. 93, no. 6, pp. 369-380. http://dx.doi.org/10.1055/s-0034-1367080. PMid:24863908.
http://dx.doi.org/10.1055/s-0034-1367080...
; Kokai et al., 2014KOKAI, L.E., MARRA, K. and RUBIN, J.P., 2014. Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Translational Research; the Journal of Laboratory and Clinical Medicine, vol. 163, no. 4, pp. 399-408. http://dx.doi.org/10.1016/j.trsl.2013.11.009. PMid:24361334.
http://dx.doi.org/10.1016/j.trsl.2013.11...
; Wainstein et al., 2018WAINSTEIN, C., QUERA, R., FLUXÁ, D., KRONBERG, U., CONEJERO, A., LÓPEZ-KÖSTNER, F., JOFRE, C. and ZARATE, A.J., 2018. Stem cell therapy in refractory perineal Crohn’s Disease: long-term Follow-up. Colorectal Disease, Ahead of print. http://dx.doi.org/10.1111/codi.14002. PMid:29316139.
http://dx.doi.org/10.1111/codi.14002...
; Bernardi, et al., 2022BERNARDI, L., SCHWEICH-ADAMI, L.C., SANTOS, C.H.M., NUNES, T.F., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2022. Evaluation of the efficacy and safety of transplantation of adipose-derived stem cells in the treatment of refractory fistulizing Crohn’s disease. Research, Social Development, vol. 11, no. 1, pp. e575111252992. http://dx.doi.org/10.33448/rsd-v11i1.25299.
http://dx.doi.org/10.33448/rsd-v11i1.252...
), in bone repair (maxilla, calvaria -severe head injury) (Kokai et al., 2014KOKAI, L.E., MARRA, K. and RUBIN, J.P., 2014. Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Translational Research; the Journal of Laboratory and Clinical Medicine, vol. 163, no. 4, pp. 399-408. http://dx.doi.org/10.1016/j.trsl.2013.11.009. PMid:24361334.
http://dx.doi.org/10.1016/j.trsl.2013.11...
), in osteoarthritis (Schweich-Adami, et al., 2021SCHWEICH-ADAMI, L.C., SILVA, R.A., BARANOSKI, A., KASSUYA, C.A.L., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2021. Efeitos das células-tronco mesenquimais no tratamento da osteoartrite de joelho: um relato de caso no Sistema Único de Saúde do Brasil. Revista Brasileira de Ortopedia, pp. S-0041-1733797. http://dx.doi.org/10.1055/s-0041-1733797.
http://dx.doi.org/10.1055/s-0041-1733797...
; Schweich-Adami, et al., 2022aSCHWEICH-ADAMI, L.C., HERMETO, L.C., CARAMALAC, S.M., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2022a. Adipose-derived stem cells in the treatment of knee osteoarthritis: from extraction methods to the preparation of the transplant. Research, Social Development, vol. 11, no. 1, pp. e24111124699. http://dx.doi.org/10.33448/rsd-v11i1.24669.
http://dx.doi.org/10.33448/rsd-v11i1.246...
, 2022bSCHWEICH-ADAMI, L.C., SILVA, R.A.D., MENEZES, J.N.D.S., BARANOSKI, A., KASSUYA, C.A.L., BERNARDI, L., JULIANO OLIVEIRA, R. and CONCEIÇÃO MILAN BROCHADO ANTONIOLLI-SILVA, A., 2022b. The intra-articular injection of adipose-derived stem cells decreases pain and reduces inflammation in knee osteoarthritis, with or without the addition of platelet-rich plasma also improves functionality. Journal of Tissue Engineering and Regenerative Medicine, vol. 16, no. 10, pp. 900-912. http://dx.doi.org/10.1002/term.3337. PMid:35797223.
http://dx.doi.org/10.1002/term.3337...
), in critical ischemia (Lee et al., 2012LEE, H.C., AN, S.G., LEE, H.W., PARK, J.S., CHA, K.S., HONG, T.J., PARK, J.H., LEE, S.Y., KIM, S.P, KIM, Y.D., CHUNG, S.W., BAE, Y.C., SHIN, Y.B., KIM, J.I. and JUNG, J.S., 2012. Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study. Circulation Journal, vol. 76, no. 7, pp. 1750-1760. http://dx.doi.org/10.1253/circj.CJ-11-1135.
http://dx.doi.org/10.1253/circj.CJ-11-11...
; Bura et al., 2014BURA, A., PLANAT-BENARD, V., BOURIN, P., SILVESTRE, J.S., GROSS, F., GROLLEAU, J.L., SAINT-LEBESE, B., PEYRAFITTE, J.A., FLEURY, S., GADELORGE, M., TAURAND, M., DUPUIS-CORONAS, S., LEOBON, B. and CASTEILLA, L., 2014. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy, vol. 6, no. 2, pp. 245-257. http://dx.doi.org/10.1016/j.jcyt.2013.11.011.
http://dx.doi.org/10.1016/j.jcyt.2013.11...
), in post-traumatic brachial plexus injury (Thakkar et al., 2014THAKKAR, U.G., VANIKAR, A.V. and TRIVEDI, H.L., 2014. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: a case report. Biomedical Journal, vol. 37, no. 4, pp. 237-240. http://dx.doi.org/10.4103/2319-4170.132893. PMid:25116721.
http://dx.doi.org/10.4103/2319-4170.1328...
) and in paraplegia after traumatic spinal cord injury (Thakkar et al., 2016THAKKAR, U.G., VANIKAR, A.V., TRIVEDI, H.L., SHAH, V.R., DAVE, S.D., DIXIT, S.B., TIWARI, B.B. and SHAH, H.H., 2016. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach. Advanced Biomedical Research, vol. 5, pp. 51. http://dx.doi.org/10.4103/2277-9175.178792. PMid:27110548.
http://dx.doi.org/10.4103/2277-9175.1787...
), have been described. However, there are no relevant reports on the use of adipose tissue-derived mesenchymal stem cells in renal and/or urological diseases. This fact reinforce the pioneering spirit of this study and our results confirm the therapeutic potential of this cell in the treatment of detrusor hypocontractility, a urological disease that is difficult to manage and treat. This is the first report of cell therapy using adipose tissue-derived mesenchymal stem cells for the treatment of DH in the SUS.

Acknowledgements

This work was carried out with support from the Federal University of Mato Grosso do Sul - UFMS / MEC - Brazil, from Hospital Maria Aparecida Pedrosian - HUMAP, and with the support of the Coordination for the Improvement of Higher Education Personnel - Brazil (Capes) - Code Funding 001. In addition to the support of the Support Foundation for the Development of Education, Science and Technology of Mato Grosso do Sul and the National Council for Scientific and Technological Development - CNPq for the Research Productivity Scholarship - PQ-2 (Process 316246/2021-2 / Grant Term 1089700081951461).

References

  • AHMED, A., FARHAN, B., VERNEZ, S. and GHONIEM, G.M., 2016. The challenges in the diagnosis of detrusor underactivity in clinical practice: a mini-review. Arab Journal of Urology, vol. 14, no. 3, pp. 223-227. http://dx.doi.org/10.1016/j.aju.2016.06.005 PMid:27547465.
    » http://dx.doi.org/10.1016/j.aju.2016.06.005
  • ANDERSON, J.B. and GRANT, J.B., 1991. Postoperative retention of urine: a prospective urodynamic study. BMJ (Clinical Research Ed.), vol. 302, no. 6781, pp. 894-896. http://dx.doi.org/10.1136/bmj.302.6781.894 PMid:1709058.
    » http://dx.doi.org/10.1136/bmj.302.6781.894
  • ASSIS, P.V., NEVES, S.C., TAKITA, L.C., TURA, B.B., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2019. Cell therapy with mesenquimial stem cells of bone marrow improves renal function in pre-clinical module. International Journal of Developmental Research, vol. 09, no. 3, pp. 26613-26619.
  • BACAKOVA, L., ZARUBOVA, J., TRAVNICKOVA, M., MUSILKOVA, J., PAJOROVA, J., SLEPICKA, P., KASALKOVA, N.S., SVORCIK, V., KOLSKA, Z., MOTARJEMI, H. and MOLITOR, M., 2018. Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review. Biotechnology Advances, vol. 36, no. 4, pp. 1111-1126. http://dx.doi.org/10.1016/j.biotechadv.2018.03.011 PMid:29563048.
    » http://dx.doi.org/10.1016/j.biotechadv.2018.03.011
  • BAYRAK, Ö. and DMOCHOWSKI, R.R., 2019. Underactive bladder: a review of the current treatment concepts. Turkish Journal of Urology, vol. 45, no. 6, pp. 401-409. http://dx.doi.org/10.5152/tud.2019.37659 PMid:30817271.
    » http://dx.doi.org/10.5152/tud.2019.37659
  • BECKER, C. and JAKSE, G., 2007. Stem cells for regeneration of urological structures. European Urology, vol. 51, no. 5, pp. 1217-1228. http://dx.doi.org/10.1016/j.eururo.2007.01.029 PMid:17254699.
    » http://dx.doi.org/10.1016/j.eururo.2007.01.029
  • BERNARDI, L., SCHWEICH-ADAMI, L.C., SANTOS, C.H.M., NUNES, T.F., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2022. Evaluation of the efficacy and safety of transplantation of adipose-derived stem cells in the treatment of refractory fistulizing Crohn’s disease. Research, Social Development, vol. 11, no. 1, pp. e575111252992. http://dx.doi.org/10.33448/rsd-v11i1.25299
    » http://dx.doi.org/10.33448/rsd-v11i1.25299
  • BURA, A., PLANAT-BENARD, V., BOURIN, P., SILVESTRE, J.S., GROSS, F., GROLLEAU, J.L., SAINT-LEBESE, B., PEYRAFITTE, J.A., FLEURY, S., GADELORGE, M., TAURAND, M., DUPUIS-CORONAS, S., LEOBON, B. and CASTEILLA, L., 2014. Phase I trial: the use of autologous cultured adipose-derived stroma/stem cells to treat patients with non-revascularizable critical limb ischemia. Cytotherapy, vol. 6, no. 2, pp. 245-257. http://dx.doi.org/10.1016/j.jcyt.2013.11.011
    » http://dx.doi.org/10.1016/j.jcyt.2013.11.011
  • D’ANCONA, C., HAYLEN, B., OELKE, M., ABRANCHES-MONTEIRO, L., ARNOLD, E., GOLDMAN, H., HAMID, R., HOMMA, Y., MARCELISSEN, T., RADEMAKERS, K., SCHIZAS, A., SINGLA, A., SOTO, I., TSE, V., DE WACHTER, S. and HERSCHORN, S., and STANDARDISATION STEERING COMMITTEE ICS AND THE ICS WORKING GROUP ON TERMINOLOGY FOR MALE LOWER URINARY TRACT & PELVIC FLOOR SYMPTOMS AND DYSFUNCTION. 2019. The International Continence Society (ICS) report on the terminology for adult male lower urinary tract and pelvic floor symptoms and dysfunction. Neurourology and Urodynamics, vol. 38, no. 2, pp. 433-477. http://dx.doi.org/10.1002/nau.23897 PMid:30681183.
    » http://dx.doi.org/10.1002/nau.23897
  • FRÖLICH, K., HAGEN, R. and KLEINSASSER, N., 2014. Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in otorhinolaryngology. Laryngo- Rhino- Otologie, vol. 93, no. 6, pp. 369-380. http://dx.doi.org/10.1055/s-0034-1367080 PMid:24863908.
    » http://dx.doi.org/10.1055/s-0034-1367080
  • GAMMIE, A., KAPER, M., DORREPAAL, C., KOS, T. and ABRAMS, P., 2016. Signs and symptoms of detrusor underactivity: an analysis of clinical presentation and urodynamic tests from a large group of patients undergoing pressure flow studies. European Urology, vol. 69, no. 2, pp. 361-369. http://dx.doi.org/10.1016/j.eururo.2015.08.014 PMid: 26318706.
    » http://dx.doi.org/10.1016/j.eururo.2015.08.014
  • HANSON, S.E., GUTOWSKI, K.A. and HEMATTI, P., 2010. Clinical applications of mesenchymal stem cells in soft tissue augmentation. Aesthetic Surgery Journal, vol. 30, no. 6, pp. 838-842. http://dx.doi.org/10.1177/1090820X10386364 PMid:21131458.
    » http://dx.doi.org/10.1177/1090820X10386364
  • KOKAI, L.E., MARRA, K. and RUBIN, J.P., 2014. Adipose stem cells: biology and clinical applications for tissue repair and regeneration. Translational Research; the Journal of Laboratory and Clinical Medicine, vol. 163, no. 4, pp. 399-408. http://dx.doi.org/10.1016/j.trsl.2013.11.009 PMid:24361334.
    » http://dx.doi.org/10.1016/j.trsl.2013.11.009
  • LEE, H.C., AN, S.G., LEE, H.W., PARK, J.S., CHA, K.S., HONG, T.J., PARK, J.H., LEE, S.Y., KIM, S.P, KIM, Y.D., CHUNG, S.W., BAE, Y.C., SHIN, Y.B., KIM, J.I. and JUNG, J.S., 2012. Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study. Circulation Journal, vol. 76, no. 7, pp. 1750-1760. http://dx.doi.org/10.1253/circj.CJ-11-1135
    » http://dx.doi.org/10.1253/circj.CJ-11-1135
  • LEVANOVICH, P.E., DIOKNO, A., HASENAU, D.L., LAJINESS, M., PRUCHNIC, R. and CHANCELLOR, M.B., 2015. Intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder: pilot study. International Urology and Nephrology, vol. 47, no. 3, pp. 465-467. http://dx.doi.org/10.1007/s11255-015-0924-1 PMid:25663053.
    » http://dx.doi.org/10.1007/s11255-015-0924-1
  • LOCKE, M., WINDSOR, J. and DUNBAR, P.R., 2009. Human adipose-derived stem cells: isolation, characterization and applications in surgery. ANZ Journal of Surgery, vol. 79, no. 4, pp. 235-244. http://dx.doi.org/10.1111/j.1445-2197.2009.04852.x PMid:19432707.
    » http://dx.doi.org/10.1111/j.1445-2197.2009.04852.x
  • NAE, S., BORDEIANU, I., STĂNCIOIU, A.T. and ANTOHI, N., 2013. Human adipose-derived stem cells: definition, isolation, tissue-engineering applications. Romanian Journal of Morphology and Embryology, vol. 54, no. 4, pp. 919-924. PMid:24398986.
  • OLIVEIRA, J.R., NEVES, S.C., REZENDE, G.C.D., MIIJI, L.N.O., PELIZARO, B.I., OLIVEIRA, D.D.M., OLIVEIRA, R.J. and ANTONIOLLI-SILVA, A.C.M.B., 2019. Cell therapy with adipose tissue mesenchymal stem cells improves the quality of the germinal epithelium in swiss mice. International Journal of Developmental Research, vol. 09, no. 3, pp. 26280-26288.
  • PESARINI, J.R., OLIVEIRA, E.J.T., PESSATTO, L.R., RABACOW, A.P.M., CAMASSOLA, M., DOS SANTOS, B.P., DE BARROS, M.E., CANTERO, W.B., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2018. Calcitriol combined with calcium chloride causes apoptosis in undifferentiated adipose tissue-derived human mesenchymal stem cells, but this effect decreases during adipogenic differentiation. Biomedicine and Pharmacotherapy, vol. 108, pp. 914-924. http://dx.doi.org/10.1016/j.biopha.2018.09.083 PMid:30372903.
    » http://dx.doi.org/10.1016/j.biopha.2018.09.083
  • REYNARD, J.M., YANG, Q., DONOVAN, J.L., PETERS, T.J., SCHAFER, W., DE LA ROSETTE, J.J., DABHOIWALA, N.F., OSAWA, D., LIM, A.T. and ABRAMS, P., 1998. The ICS-‘BPH’Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction. British Journal of Urology, vol. 82, no. 5, pp. 619-623. http://dx.doi.org/10.1046/j.1464-410X.1998.00813.x PMid:9839573.
    » http://dx.doi.org/10.1046/j.1464-410X.1998.00813.x
  • SCHWEICH-ADAMI, L.C., HERMETO, L.C., CARAMALAC, S.M., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2022a. Adipose-derived stem cells in the treatment of knee osteoarthritis: from extraction methods to the preparation of the transplant. Research, Social Development, vol. 11, no. 1, pp. e24111124699. http://dx.doi.org/10.33448/rsd-v11i1.24669
    » http://dx.doi.org/10.33448/rsd-v11i1.24669
  • SCHWEICH-ADAMI, L.C., SILVA, R.A., BARANOSKI, A., KASSUYA, C.A.L., ANTONIOLLI-SILVA, A.C.M.B. and OLIVEIRA, R.J., 2021. Efeitos das células-tronco mesenquimais no tratamento da osteoartrite de joelho: um relato de caso no Sistema Único de Saúde do Brasil. Revista Brasileira de Ortopedia, pp. S-0041-1733797. http://dx.doi.org/10.1055/s-0041-1733797
    » http://dx.doi.org/10.1055/s-0041-1733797
  • SCHWEICH-ADAMI, L.C., SILVA, R.A.D., MENEZES, J.N.D.S., BARANOSKI, A., KASSUYA, C.A.L., BERNARDI, L., JULIANO OLIVEIRA, R. and CONCEIÇÃO MILAN BROCHADO ANTONIOLLI-SILVA, A., 2022b. The intra-articular injection of adipose-derived stem cells decreases pain and reduces inflammation in knee osteoarthritis, with or without the addition of platelet-rich plasma also improves functionality. Journal of Tissue Engineering and Regenerative Medicine, vol. 16, no. 10, pp. 900-912. http://dx.doi.org/10.1002/term.3337 PMid:35797223.
    » http://dx.doi.org/10.1002/term.3337
  • STERODIMAS, A., DE FARIA, J., NICARETTA, B. and PITANGUY, I., 2010. Tissue engineering with adipose-derived stem cells (ADSCs): current and future applications. Journal of Plastic, Reconstructive & Aesthetic Surgery; JPRAS, vol. 63, no. 11, pp. 1886-1892. http://dx.doi.org/10.1016/j.bjps.2009.10.028 PMid:19969517.
    » http://dx.doi.org/10.1016/j.bjps.2009.10.028
  • TAMANINI, J.T., DAMBROS, M., D’ANCONA, C.A., PALMA, P.C. and RODRIGUES NETTO JUNIOR, N., 2004. Validação para o português do “International Consultation on Incontinence Questionnaire -- Short Form” (ICIQ-SF). Revista de Saude Publica, vol. 38, no. 3, pp. 438-444. http://dx.doi.org/10.1590/S0034-89102004000300015 PMid:15243675.
    » http://dx.doi.org/10.1590/S0034-89102004000300015
  • TEUNISSEN, D., VAN DEN BOSCH, W., VAN WEEL, C. and LAGRO-JANSSEN, T., 2006. “It can always happen”: the impact of urinary incontinence on elderly men and women. Scandinavian Journal of Primary Health Care, vol. 24, no. 3, pp. 166-173. http://dx.doi.org/10.1080/02813430600739371 PMid:16923626.
    » http://dx.doi.org/10.1080/02813430600739371
  • THAKKAR, U.G., VANIKAR, A.V. and TRIVEDI, H.L., 2014. Co-infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and bone marrow derived hematopoietic stem cells, a viable therapy for post-traumatic brachial plexus injury: a case report. Biomedical Journal, vol. 37, no. 4, pp. 237-240. http://dx.doi.org/10.4103/2319-4170.132893 PMid:25116721.
    » http://dx.doi.org/10.4103/2319-4170.132893
  • THAKKAR, U.G., VANIKAR, A.V., TRIVEDI, H.L., SHAH, V.R., DAVE, S.D., DIXIT, S.B., TIWARI, B.B. and SHAH, H.H., 2016. Infusion of autologous adipose tissue derived neuronal differentiated mesenchymal stem cells and hematopoietic stem cells in post-traumatic paraplegia offers a viable therapeutic approach. Advanced Biomedical Research, vol. 5, pp. 51. http://dx.doi.org/10.4103/2277-9175.178792 PMid:27110548.
    » http://dx.doi.org/10.4103/2277-9175.178792
  • TOBITA, M., ORBAY, H. and MIZUNO, H., 2011. Adipose-derived stem cells: current findings and future perspectives. Discovery Medicine, vol. 11, no. 57, pp. 160-170. PMid:21356171.
  • WAINSTEIN, C., QUERA, R., FLUXÁ, D., KRONBERG, U., CONEJERO, A., LÓPEZ-KÖSTNER, F., JOFRE, C. and ZARATE, A.J., 2018. Stem cell therapy in refractory perineal Crohn’s Disease: long-term Follow-up. Colorectal Disease, Ahead of print. http://dx.doi.org/10.1111/codi.14002 PMid:29316139.
    » http://dx.doi.org/10.1111/codi.14002
  • ZERATI, F.M., NARDOZZA, J.A. and REIS, R.B., 2010. Urologia fundamental São Paulo: Planmark. 274 p.

Publication Dates

  • Publication in this collection
    28 Apr 2023
  • Date of issue
    2023

History

  • Received
    10 Oct 2022
  • Accepted
    27 Feb 2023
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