Dataset Information

A preclinical study-systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue.

ABSTRACT:

Background

Mounting evidence has shown that a novel subset of mesenchymal stem cells (MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells (GMSCs) displays a greater immunotherapeutic potential and regenerative repair expression than MSCs obtained from other tissues. However, the safety of the use of transplanted GMSCs in humans remains unclear.

Methods

In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagle dog, and monkey as well as two animal models of autoimmune diseases.

Results

In short- and long-term toxicity tests, infused GMSCs had no remarkable adverse effects on hematologic and biochemical indexes, particularly on the major organs such as heart, liver, spleen, and kidney in recipient animals. It was also shown that GMSCs were well tolerated in other assays including hemolysis, vascular, and muscular stimulation, as well as systemic anaphylaxis and passive skin Arthus reaction in animal models. GSMC infusion did not cause any notable side effects on animal models of either autoimmune arthritis or lupus. Significantly, GMSCs most likely play no role in genotoxicity and tumorigenesis. The biological features remained stable for an extended period after cell transfer.

Conclusions

GMSCs are safe in various animal models of autoimmunity, even during active disease episodes, especially in monkeys. This study paves a solid road for future clinical trials of GMSCs in patients with autoimmune and inflammatory diseases.

SUBMITTER: Zhao J

PROVIDER: S-EPMC6567625 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

A preclinical study-systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue.

Zhao Jun J Wang Julie J Dang Junlong J Zhu Wangyu W Chen Yaqiong Y Zhang Ximei X Xie Junliang J Hu Bo B Huang Feng F Sun Baoqing B Bellanti Joseph A JA Zheng Song Guo SG

Stem cell research & therapy 20190613 1

<h4>Background</h4>Mounting evidence has shown that a novel subset of mesenchymal stem cells (MSCs) derived from human gingiva referred to as gingival mesenchymal stem cells (GMSCs) displays a greater immunotherapeutic potential and regenerative repair expression than MSCs obtained from other tissues. However, the safety of the use of transplanted GMSCs in humans remains unclear.<h4>Methods</h4>In this study, we evaluated the safety of GMSCs transplanted into mouse, rat, rabbit, beagle dog, and ...[more]

PMID: 31196163

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Project description:BackgroundEvidence has demonstrated conditioned medium (CM) from periodontal ligament stem cells (PDLSCs) improved periodontal regeneration. Gingival mesenchymal stem cells (GMSCs) have been considered an alternative strategy for regenerative medicine. To determine whether GMSC-CM could promote periodontal wound healing, we compared the effects of GMSC-CM and PDLSC-CM on periodontal regeneration and the underlying mechanisms in rat periodontal defects.MethodsCell-free CMs were collected from PDLSCs, GMSCs, and gingival fibroblasts (GFs) using ultracentrifugation (100-fold concentration). Periodontal defects were created on the buccal side of the first molar in the left mandible of 90 rats by a surgical method. Collagen membranes loaded with concentrated CMs (α-MEM, GF-CM, GMSC-CM, PDLSC-CM) were transplanted into periodontal defects. After 1, 2, and 4 weeks, the animals were sacrificed and specimens including the first molar and the surrounding tissues were separated and decalcified. Hematoxylin-eosin and Masson's trichrome staining were performed to evaluate periodontal regeneration. Immunohistochemical staining for tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-10 was conducted to analyze inflammation. Immunohistochemistry of BSP-II and Runx2 was performed to analyze osteoblast differentiation.ResultsHistological analysis showed the amount of newly formed periodontal tissue was significantly higher in both the GMSC-CM and PDLSC-CM groups than in the other groups, with no significant difference between these two groups. At 1 and 2 weeks, the expression levels of TNF-α and IL-1β were significantly lower in the GMSC-CM and PDLSC-CM groups than in the other three groups, while there was no significant difference between these two groups. IL-10 expression was significantly higher in the GMSC-CM group than in the PDLSC-CM group and the other three groups. At 1, 2, and 4 weeks, BSP-II and Runx2 expressions were significantly higher in the GMSC-CM and PDLSC-CM groups than in the other three groups, with no significant difference between the two groups.ConclusionsOur results demonstrate that GMSC-CM transplantation can significantly promote periodontal regeneration in rats and achieve the same effect as PDLSC-CM. The mechanism of periodontal regeneration may involve the regulation of inflammatory factors and the promotion of osteogenic differentiation of bone progenitor cells in the wound region by CMs from MSCs.

Dataset Information

A preclinical study-systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue.

Background

Methods

Results

Conclusions

Publications

A preclinical study-systemic evaluation of safety on mesenchymal stem cells derived from human gingiva tissue.

Similar Datasets

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