Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

Park, Yu Mi; Yang, Chang Mo; Cho, Hee Yeon

doi:10.3390/ijms23136877

Cited by 4 publications

(1 citation statement)

References 69 publications

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“…While bone marrow and adipose tissue are the most studied, other sources for the differentiation of MSCs into IPCs were also reported. These include umbilical cord [ 67 ] amniotic fluid [ 68 ], Wharton’s jelly [ 69 ], and dental pulp [ 70 ]. Stored umbilical cord-derived MSCs can serve as an autologous source for their donors in case of future need.…”

Section: Mesenchymal Stem/stromal Cells (Mscs)mentioning

confidence: 99%

Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration

Ghoneim,

Gabr,

El-Halawani

et al. 2024

Stem Cell Res Ther

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Over the past decade, there had been progress in the development of cell therapy for insulin-dependent diabetes. Nevertheless, important hurdles that need to be overcome still remain. Protocols for the differentiation of pluripotent stem cells into pancreatic progenitors or fully differentiated β-cells have been developed. The resulting insulin-producing cells can control chemically induced diabetes in rodents and were the subject of several clinical trials. However, these cells are immunogenic and possibly teratogenic for their transplantation, and an immunoisolation device and/or immunosuppression is needed. A growing number of studies have utilized genetic manipulations to produce immune evasive cells. Evidence must be provided that in addition to the expected benefit, gene manipulations should not lead to any unforeseen complications. Mesenchymal stem/stromal cells (MSCs) can provide a viable alternative. MSCs are widely available from many tissues. They can form insulin-producing cells by directed differentiation. Experimentally, evidence has shown that the transplantation of allogenic insulin-producing cells derived from MSCs is associated with a muted allogeneic response that does not interfere with their functionality. This can be explained by the immunomodulatory functions of the MSC subpopulation that did not differentiate into insulin-producing cells. Recently, exosomes derived from naive MSCs have been used in the experimental domain to treat diabetes in rodents with varying degrees of success. Several mechanisms for their beneficial functions were proposed including a reduction in insulin resistance, the promotion of autophagy, and an increase in the T regulatory population. However, euglycemia was not achieved in any of these experiments. We suggest that exosomes derived from β-cells or insulin-producing cells (educated) can provide a better therapeutic effect than those derived from undifferentiated cells.

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Section: Mesenchymal Stem/stromal Cells (Mscs)mentioning

confidence: 99%

Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration

Ghoneim,

Gabr,

El-Halawani

et al. 2024

Stem Cell Res Ther

View full text Add to dashboard Cite

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Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges

Zou,

Li,

Chen

et al. 2023

Endocrine

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Innovations in bio-engineering and cell-based approaches to address immunological challenges in islet transplantation

Ho,

Teo,

2024

Front. Immunol.

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Human allogeneic pancreatic islet transplantation is a life-changing treatment for patients with severe Type 1 Diabetes (T1D) who suffer from hypoglycemia unawareness and high risk of severe hypoglycemia. However, intensive immunosuppression is required to prevent immune rejection of the graft, that may in turn lead to undesirable side effects such as toxicity to the islet cells, kidney toxicity, occurrence of opportunistic infections, and malignancies. The shortage of cadaveric human islet donors further limits islet transplantation as a treatment option for widespread adoption. Alternatively, porcine islets have been considered as another source of insulin-secreting cells for transplantation in T1D patients, though xeno-transplants raise concerns over the risk of endogenous retrovirus transmission and immunological incompatibility. As a result, technological advancements have been made to protect transplanted islets from immune rejection and inflammation, ideally in the absence of chronic immunosuppression, to improve the outcomes and accessibility of allogeneic islet cell replacement therapies. These include the use of microencapsulation or macroencapsulation devices designed to provide an immunoprotective environment using a cell-impermeable layer, preventing immune cell attack of the transplanted cells. Other up and coming advancements are based on the use of stem cells as the starting source material for generating islet cells ‘on-demand’. These starting stem cell sources include human induced pluripotent stem cells (hiPSCs) that have been genetically engineered to avoid the host immune response, curated HLA-selected donor hiPSCs that can be matched with recipients within a given population, and multipotent stem cells with natural immune privilege properties. These strategies are developed to provide an immune-evasive cell resource for allogeneic cell therapy. This review will summarize the immunological challenges facing islet transplantation and highlight recent bio-engineering and cell-based approaches aimed at avoiding immune rejection, to improve the accessibility of islet cell therapy and enhance treatment outcomes. Better understanding of the different approaches and their limitations can guide future research endeavors towards developing more comprehensive and targeted strategies for creating a more tolerogenic microenvironment, and improve the effectiveness and sustainability of islet transplantation to benefit more patients.

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Therapeutic Effects of Insulin-Producing Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Type 1 Diabetes Mouse Model

Cited by 4 publications

References 69 publications

Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration

Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration

Urine-derived stem cell therapy for diabetes mellitus and its complications: progress and challenges

Innovations in bio-engineering and cell-based approaches to address immunological challenges in islet transplantation

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