Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy

Ding, Dah‐Ching; Chang, Yung Hsien; Shyu, Woei Cherng; Lin, Shinn Zong

doi:10.3727/096368915x686841

Cited by 454 publications

(359 citation statements)

References 75 publications

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“…The authors suggested that MSC plasticity was linked with the expression of early differentiation markers. MSCs from various sources are able to differ entiate not only in mesoderm lineages, but into ecto derm and endoderm derivatives (Huang et al, 2010;Antonucci et al, 2011;Mamidi et al, 2011;Ding et al, 2015). It has been demonstrated that human bone marrow MSCs expressed biologically active compounds that modified the microenvironment in the damaged tissue and facilitated tissue repair (Caplan, Dennis, 2006;Phinney, 2007;Tan et al, 2011).…”

Section: Surface Marker Expression In Fetmsc and Fetmsc And Their Sphmentioning

confidence: 98%

Cellular spheroids obtained from mesenchymal stem cells derived from bone marrow and limb muscle of early human embryo

et al. 2015

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Cellular spheroids were obtained from mesenchymal stem cells derived from different tissues of 5 to 6 week old embryos: bone marrow (FetMSC) and limb muscle (M FetMSC). The properties of these cells maintained in monolayer (2D cultivation) or spheroids (3D cultivation) were compared. Cellular sphe roids were obtained from monolayer cultures at the sixth passage after decryopreservation and assayed 48 h after their formation. Unlike monolayer cultures, spheroids are heterogeneous cell populations consisted of fibroblast like and epithelioid cells. Two day old spheroids are actively proliferating structures. Cell surface markers were analyzed by flow cytometry. Monolayer culture and cellular spheroids expressed CD44, CD73, CD90, CD105, and HLA ABC common for mesenchymal stem cells (MSCs) and lacked CD34 and HLA DR. However, expression of CD90 and CD105 antigens was significantly lower in spheroids than in mono layer cultures. Expression of transcription factors and surface antigens typical for human embryonic stem cells were analyzed with immunofluorescence and flow cytometry. Expression of Sox 2 and SSEA 4 in 2D and 3D cultures, lack of Oct 4 in 2D cultures, and its increase in 3D cultures were found. Both monolayer cells and spheroids were able to differentiate into osteogenic, chondrogenic, and adipogenic lineages, although monolayer cultures and spheroids differed. Adipogenic differentiation was more active in the cellular spheroids from M FetMSC cells compared to corresponding monolayer cultures. Differences between the 2D and 3D cultures of both lines have been shown by the character of chondrogenic differentiation. As a whole, these findings confirm the MSC status for the cellular spheroids derived from FetMSC and M FetMSC mono layer cultures and attest to their increased differentiation potential compared to monolayer cultures.Abbreviations: ECM-extracellular matrix, MSC-mesenchy mal stem cell, ESC-embryonic stem cell, 2D-two dimen sional culture system, 3D-three dimensional culture system. 432 CELL AND TISSUE BIOLOGY Vol. 9No. 6 2015 KRYLOVA et al.

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Section: Surface Marker Expression In Fetmsc and Fetmsc And Their Sphmentioning

confidence: 98%

Cellular spheroids obtained from mesenchymal stem cells derived from bone marrow and limb muscle of early human embryo

et al. 2015

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“…Regarding their therapeutic value, storage banking system and protocols should be established immediately. Ding et al [18]. critically evaluates their therapeutic value, challenges, and future directions for their clinical applications.…”

Section: Discussionmentioning

confidence: 99%

Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

Ruan

Xiang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Stem cell-based therapy is attractive in many clinical studies, but current data on the safety of stem cell applications remains inadequate. This study observed the safety, immunological effect of cynomolgus monkey umbilical cord mesenchymal stem cells (mUC-MSCs) injected into cynomolgus monkeys, in order to evaluate the safety of human umbilical cord mesenchymal stem cells (hUC-MSCs) prepared for human clinical application. Methods: Eighteen cynomolgus monkeys were divided into three groups. Group 1 is control group, Group 2 is low-dose group, Group 3 is high-dose group. After repeated administrations of mUC-MSCs, cynomolgus monkeys were observed for possible toxic reactions. Results: During the experiment, no animal died. There were no toxicological abnormalities in body weight, body temperature, electrocardiogram, coagulation and pathology. In the groups 2 and 3, AST and CK transiently increased, and serum inorganic P slightly decreased. All animals were able to recover at 28 days after the infusion was stopped. In the groups 2 and 3, CD3⁺ and IL-6 levels significantly increased, and recovery was after 28 days of infusion. There were no obvious pathological changes associated with the infusion of cells in the general and microscopic examinations. Conclusions: The safe dosage of repeated intravenous infusion of mUC-MSCs in cynomolgus monkeys is 1.0 × 10⁷/kg, which is 10 times of that in clinical human use.

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“…15 WJ-MSC secrete large amounts of cytokines, and are non-oncogenic; thus, they are an ideal source of MSC for cell therapies. 16,17 WJ-MSC play a role in immune regulation through direct contact or secretion of cytokines. 18 However, the application of WJ-MSC in spontaneous abortion has not been reported.…”

mentioning

confidence: 99%

Therapeutic effects of Wharton jelly‐derived mesenchymal stem cells on rat abortion models

Chen

Yang

et al. 2016

J of Obstet and Gynaecol

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Aim: The aim of this study was to investigate the therapeutic effects and mechanism of Wharton jelly-derived mesenchymal stem cells (WJ-MSC) in a spontaneous-abortion rat model. Methods: An abortion model was established using intravenous injection of bromocriptine. WJ-MSC were isolated and cultured from Wharton jelly of the human umbilical cord. The pathologic changes of placenta decidual tissues were observed after hematoxylin-eosin staining. The embryo absorption rate was counted. The protein and mRNA levels of interleukin (IL)-10, interferon (IFN)-γ and IL-17 in each group were tested by enzyme-linked immunosorbent assay, Western blot and quantitative real-time polymerase chain reaction. Results: After bromocriptine injection, decidual cells degenerated and the connections between them loosened. Furthermore, some of the decidual cells were necrotic and the nuclei had disappeared. However, the transplantation of a large population of WJ-MSC prevented these damages from occurring. The changes of levels of IL-10, IFN-γ and IL-17 in serum and placenta decidual tissues induced by bromocriptine were well restored by a high, but not a low, dose of WJ-MSC engraft. Conclusion: WJ-MSC can ameliorate early pregnancy loss. The mechanism may be related to its upregulation of IL-10 and downregulation of IFN-γ and IL-17.

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Human Umbilical Cord Mesenchymal Stem Cells: A New Era for Stem Cell Therapy

Cited by 454 publications

References 75 publications

Cellular spheroids obtained from mesenchymal stem cells derived from bone marrow and limb muscle of early human embryo

Cellular spheroids obtained from mesenchymal stem cells derived from bone marrow and limb muscle of early human embryo

Chronic Toxicity Test in Cynomolgus Monkeys For 98 Days with Repeated Intravenous Infusion of Cynomolgus Umbilical Cord Mesenchymal Stem Cells

Therapeutic effects of Wharton jelly‐derived mesenchymal stem cells on rat abortion models

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