Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice

Bertera, Suzanne; Knöll, Martin; Knoll, Carmela A.; Hara, Hidetaka; Kimbrel, Erin A.; Kouris, Nickolas A.; Lanza, Robert; Philips, Brett E.; Garciafigueroa, Yesica; Giannoukakis, Nick; Cooper, David K. C.; Trucco, Massimo; Bottino, Rita

doi:10.3389/fmed.2021.660877

Cited by 2 publications

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“…Additionally, mice transplanted intraperitoneally with human islets coencapsulated with MSCs in hydrogel microspheres, composed of calcium alginate and covalently crosslinked to polyethylene glycol showed significantly lower blood glucose levels and prolonged islet graft survival (57). Others have shown that improved graft function correlates with enhanced revascularization of islets transplanted under the kidney capsule (68)(69)(70). Accordingly, research findings revealed significantly higher apoptosis rates in islet cells cultured without MSCs (16).…”

Section: Co-transplantation Of Islets With Mscs From Different Sourcesmentioning

confidence: 99%

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function

et al. 2022

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Type 1 diabetes (T1D) is a widespread disease, affecting approximately 41.5 million people worldwide. It is generally treated with exogenous insulin, maintaining physiological blood glucose levels but also leading to long-term therapeutic complications. Pancreatic islet cell transplantation offers a potential alternative treatment to insulin injections. Shortage of human organ donors has raised the interest for porcine islet xenotransplantation. Neonatal porcine islets are highly available, can proliferate and mature in vitro as well as after transplantation in vivo. Despite promising preclinical results, delayed insulin secretion caused by immaturity and immunogenicity of the neonatal porcine islets remains a challenge for their clinical application. Multipotent mesenchymal stromal cells (MSCs) are known to have pro-angiogenic, anti-inflammatory and immunomodulatory effects. The current state of research emphasizes the great potential of co-culture and co-transplantation of islet cells with MSCs. Studies have shown enhanced islet proliferation and maturation, insulin secretion and graft survival, resulting in an improved graft outcome. This review summarizes the immunomodulatory and anti-inflammatory properties of MSC in the context of islet transplantation.

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Section: Co-transplantation Of Islets With Mscs From Different Sourcesmentioning

confidence: 99%

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function

et al. 2022

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A brief review of the current status of pig islet xenotransplantation

Cooper,

Mou,

Bottino

2024

Front. Immunol.

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An estimated 1.5 million Americans suffer from Type I diabetes mellitus, and its incidence is increasing worldwide. Islet allotransplantation offers a treatment, but the availability of deceased human donor pancreases is limited. The transplantation of islets from gene-edited pigs, if successful, would resolve this problem. Pigs are now available in which the expression of the three known xenoantigens against which humans have natural (preformed) antibodies has been deleted, and in which several human ‘protective’ genes have been introduced. The transplantation of neonatal pig islets has some advantages over that of adult pig islets. Transplantation into the portal vein of the recipient results in loss of many islets from the instant blood-mediated inflammatory reaction (IBMIR) and so the search for an alternative site continues. The adaptive immune response can be largely suppressed by an immunosuppressive regimen based on blockade of the CD40/CD154 T cell co-stimulation pathway, whereas conventional therapy (e.g., based on tacrolimus) is less successful. We suggest that, despite the need for effective immunosuppressive therapy, the transplantation of ‘free’ islets will prove more successful than that of encapsulated islets. There are data to suggest that, in the absence of rejection, the function of pig islets, though less efficient than human islets, will be sufficient to maintain normoglycemia in diabetic recipients. Pig islets transplanted into immunosuppressed nonhuman primates have maintained normoglycemia for periods extending more than two years, illustrating the potential of this novel form of therapy.

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Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice

Cited by 2 publications

References 51 publications

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function

Multipotent Mesenchymal Stromal Cells Interact and Support Islet of Langerhans Viability and Function

A brief review of the current status of pig islet xenotransplantation

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