<b>Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy?</b>

Alves, Ana Karina Soares; Lanzoni, Valéria; Fuziy, Rogério Aoki; Franco, Rita Maria Aparecida Monteiro Moura; Maeda, Carlos Toshinori; Lopes, Gaspar de Jesus; Linhares, Marcelo Moura

doi:10.1590/s0102-865020170070000002

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ORIGINAL ARTICLES, 2-Experimental Surgery • Acta Cir. Bras. 32 (07) • July 2017 • https://doi.org/10.1590/s0102-865020170070000002 linkcopy

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy? ¹

Authorship SCIMAGO INSTITUTIONS RANKINGS

Purpose: To evaluate the effects of mesenchymal stem cells on liver regeneration in rats following a 70% hepatectomy.

Methods: Forty rats were subjected to 70% hepatectomy and then ~10⁶ mesenchymal stem cells (test group), or saline solution (control group), were infused into their livers via the portal vein. Each treatment group was divided into early and late subgroups (euthanized 3 d and 5 d following the operation, respectively). Group comparisons of Albumin, aminotransaminases (AST, ALT), and Alcaline Phosphatase (AP) levels, proliferative index (ki-67+ straining), and mitotic cell counts were conducted.

Results: No significant differences in liver regeneration rate, number of mitoses, proliferative index, or serum levels of albumin, AST, or AP were observed. ALT levels were higher in the test group than in the control group (p<.05).

Conclusions: Mesenchymal stem-cell therapy did not improve liver regeneration rate 3 d or 5 d after 70% hepatectomy in rats. Likewise, the therapy appeared not to affect liver function, proliferative index, or number of mitoses significantly.

Key words:
Mesenchymal Stem Cell Transplantation; Liver Regeneration; Hepatectomy; Cell- and Tissue-Based Therapy; Rats

Authorship

person Ana Karina Soares Alves

schoolFellow Master degree, Postgraduate Program in Interdisciplinary Surgical Sciences, Universidade Federal de São Paulo (UNIFESP), Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; final approval of the version to be published.Universidade Federal de São PauloBrazilBrazilFellow Master degree, Postgraduate Program in Interdisciplinary Surgical Sciences, Universidade Federal de São Paulo (UNIFESP), Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; final approval of the version to be published.

person Valéria Lanzoni

schoolPhD, Department of Pathology, UNIFESP, Sao Paulo-SP, Brazil. Acquisition, analysis and interpretation of data; final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Department of Pathology, UNIFESP, Sao Paulo-SP, Brazil. Acquisition, analysis and interpretation of data; final approval of the version to be published.

person Rogério Aoki Fuziy

schoolAssociate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilAssociate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.

person Rita Maria Aparecida Monteiro Moura Franco

person Carlos Toshinori Maeda

person Gaspar de Jesus Lopes Filho

schoolPhD, Chairman, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Chairman, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.

person Marcelo Moura Linhares

schoolPhD, Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article; final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article; final approval of the version to be published.

Correspondence: Marcelo Moura Linhares Rua Leandro Dupre, 334 04025-002 São Paulo - SP Brasil Tel.: (55 11)5531-3621/98126-1188
emailmlinhares@unifesp.br

Conflict of interest:

none

SCIMAGO INSTITUTIONS RANKINGS

Fellow Master degree, Postgraduate Program in Interdisciplinary Surgical Sciences, Universidade Federal de São Paulo (UNIFESP), Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; final approval of the version to be published.Universidade Federal de São PauloBrazilBrazilFellow Master degree, Postgraduate Program in Interdisciplinary Surgical Sciences, Universidade Federal de São Paulo (UNIFESP), Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; final approval of the version to be published.

PhD, Department of Pathology, UNIFESP, Sao Paulo-SP, Brazil. Acquisition, analysis and interpretation of data; final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Department of Pathology, UNIFESP, Sao Paulo-SP, Brazil. Acquisition, analysis and interpretation of data; final approval of the version to be published.

Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilAssociate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.

PhD, Chairman, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Chairman, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Intellectual content of the study, final approval of the version to be published.

PhD, Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article; final approval of the version to be published.UNIFESPBrazilSao Paulo, SP, BrazilPhD, Associate Professor, Division of Surgical Gastroenterology, Department of Surgery, UNIFESP, Sao Paulo-SP, Brazil. Conception and design of the study; acquisition, analysis and interpretation of data; drafting the article; final approval of the version to be published.

Figures | Tables | Formulas

Figures (1)
Tables (4)
Formulas (1)

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Figure 1 Demonstrative draft of the surgeries: A. First surgery showing the initial total liver (IT), the initial ressected liver (RL) and the liver remnant (Rem); B. The eutanasia surgery indicating the liver regeneration (LR), liver remnant (Rem) and total liver regenerated (TR).

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Table 1 Comparison of the variations in the levels of AF, AST, ALT, and albumin detected between the test and control groups on the third post-operative day.

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Table 2 Comparison of the variations in the levels of AF, AST, ALT, and albumin detected between the test and control groups on the fifth post-operative day.

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Table 3 Evaluation of the proliferative index (Ki-67) and mitotic index for the test and control groups on the third post-operative day.

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Table 4 Evaluation of the proliferative index (Ki-67) and the mitotic index for the test and control groups on the fifth day following surgery and infusion.

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imageFigure 1 Demonstrative draft of the surgeries: A. First surgery showing the initial total liver (IT), the initial ressected liver (RL) and the liver remnant (Rem); B. The eutanasia surgery indicating the liver regeneration (LR), liver remnant (Rem) and total liver regenerated (TR). open_in_new

table_chartTable 1 Comparison of the variations in the levels of AF, AST, ALT, and albumin detected between the test and control groups on the third post-operative day.

Variation (∆) 3rd post-op minus pre-op	control						test						U	p
Variation (∆) 3rd post-op minus pre-op	N	Mean	SD	Median	Min	Max	N	Mean	SD	Median	Min	Max
AF	7	92.4	66.2	82.7	21.9	200	9	44.8	36.9	39.9	-6.5	100	18	0.153
AST	6	20.6	24.6	22.3	-13.5	51.5	8	75.0	77.8	49.1	19.2	257.7	9	0.053
ALT	7	17.6	19.3	20	0	50	9	94.9	56.4	99.9	16.7	200.1	5	0.005*
Albumin	7	-19.5	6.0	-21.3	-29.2	-12	9	-17.9	10.3	-12.8	-38.9	-6.4	23	0.368

Post-op: post-operative day; Pre-op: pre-operative

table_chartTable 2 Comparison of the variations in the levels of AF, AST, ALT, and albumin detected between the test and control groups on the fifth post-operative day.

Variation (∆) 5th post-op minus pre-op	control				test				U			p
Variation (∆) 5th post-op minus pre-op	N	Mean	SD	Median	Min	Max	N	Mean	SD	Median	Min	Max
AF	10	44.9	32.4	43.0	13.5	120	10	35.80	24.8	36.6	-6.7	76	44	0.650
AST	10	48.8	54.5	40.6	-29.1	173.1	10	31.0	32.3	27.9	-12.9	81.5	40.5	0.473
ALT	10	6.4	51.9	17.0	-100	100	10	41.7	23.7	33.3	20	99.9	20	0.023*
Albumin	10	-19.5	8.7	-20.6	-30.2	-3.8	10	-16.9	7.05	-18.1	-28	-3.6	39	0.406

Post-op: post-operative day; Pre-op: pre-operative

table_chartTable 3 Evaluation of the proliferative index (Ki-67) and mitotic index for the test and control groups on the third post-operative day.

Variables	control						test						U	p
Variables	N	Mean	SD	Median	Min	Max	N	Mean	SD	Median	Min	Max
Ki67	7	0.44	0.15	0.41	0.26	0.62	9	0.3	0.19	0.39	0.14	0.69	27	0.634
Mitotic Index	7	6.29	4.42	5.00	2.00	14.00	9	5.11	2.09	5.00	3.00	10.00	30	0.872

table_chartTable 4 Evaluation of the proliferative index (Ki-67) and the mitotic index for the test and control groups on the fifth day following surgery and infusion.

Variables	control						test						U	p
Variables	N	Mean	SD	Median	Min	Max	N	Mean	SD	Median	Min	Max
Ki67	10	0.10	0.08	0.0983	0.02	0.28	10	0.16	0.08	0.1412	0.05	0.28	30	0.131
Mitotic Index	10	1.00	0.67	1.00	0.00	2.00	10	0.60	0.52	1.00	0.00	1.00	34	0.165

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Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy? 1

Does mesenchymal stem cell improve the liver regeneration after the 70% hepatectomy? ¹