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Co‐transplantation of human adipose‐derived mesenchymal stem cells with neonatal porcine islets within a prevascularized subcutaneous space augments the xenograft function
Author(s) -
Kuppan Purushothaman,
Seeberger Karen,
Kelly Sandra,
Rosko Mandy,
Adesida Adetola,
Pepper Andrew R.,
Korbutt Gregory S.
Publication year - 2020
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12581
Subject(s) - islet , mesenchymal stem cell , transplantation , medicine , adipose tissue , insulin , immune system , immunology , renal capsule , type 1 diabetes , endocrinology , diabetes mellitus , cancer research , pathology
Background Cell transplantation has been widely recognized as a curative treatment strategy for variety of diseases including type I diabetes (T1D). Broader patient inclusion for this therapeutic option is restricted by a limited supply of healthy human islet donors and significant loss of islets immediately postintrahepatic transplant due to immune activation. Neonatal porcine islets (NPIs) are a potential ubiquitous β‐cell source for treating T1D. Mesenchymal stem cells (MSCs) have the inherent capacity to secrete immunoregulatory, anti‐inflammatory, and proangiogenic factors and, thus, have the potential to improve islet engraftment, survival, and function. Methods Herein, we assessed the effect of human adipose–derived MSCs (AdMSCs) on NPI metabolic outcomes in diabetic mice when co‐transplanted within the prevascularized subcutaneous deviceless (DL) space or kidney capsule (KC). Graft function has been evaluated by weekly blood glucose, stimulated porcine insulin, glucose tolerance, and total cellular graft insulin content. Results Compared with NPI alone, co‐transplantation of NPIs and AdMSCs resulted in significantly earlier normoglycemia (* P < .05), improved glucose tolerance (* P < .05), superior stimulated serum porcine insulin (** P < .01), and increased graft insulin content (* P < .05) in the DL site and not the KC. Conclusions Thus, our study demonstrates that co‐transplantation of human AdMSCs with NPIs is an effective tactic to augment islet xenograft function in a clinically relevant extrahepatic site.