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

Autor:	Bertera S; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States., Knoll MF; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States., Knoll C; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States., Hara H; Department of Surgery, Xenotransplantation Program, University of Alabama at Birmingham, Birmingham, AL, United States., Kimbrel EA; Astellas Institute for Regenerative Medicine, Westborough, MA, United States., Kouris NA; Astellas Institute for Regenerative Medicine, Westborough, MA, United States., Lanza R; Astellas Institute for Regenerative Medicine, Westborough, MA, United States., Philips BE; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States., Garciafigueroa Y; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States., Giannoukakis N; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States.; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States., Cooper DKC; Department of Surgery, Xenotransplantation Program, University of Alabama at Birmingham, Birmingham, AL, United States., Trucco M; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States.; Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, United States., Bottino R; Institute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2021 Apr 15; Vol. 8, pp. 660877. Date of Electronic Publication: 2021 Apr 15 (Print Publication: 2021).
DOI:	10.3389/fmed.2021.660877
Abstrakt:	Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function. However, experimental data can be inconsistent due to variables associated with MSC generation (including donor characteristics and tissue source), thus, demonstrating the need for a well-characterized and uniform cell product before translation to the clinic. Unlike bone marrow- or adipose tissue-derived MSCs, human embryonic stem cell-derived-MSCs (hESC-MSCs) offer an unlimited source of stable and highly-characterized cells that are easily scalable. Here, we studied the effects of human hemangioblast-derived mesenchymal cells (HMCs), (i.e., MSCs differentiated from hESCs using a hemangioblast intermediate), on islet cell transplantation using a minimal islet mass model. The co-transplantation of the HMCs allowed a mass of islets that was insufficient to correct diabetes on its own to restore glycemic control in all recipients. Our in vitro studies help to elucidate the mechanisms including reduction of cytokine stress by which the HMCs support islet graft protection in vivo . Derivation, stability, and scalability of the HMC source may offer unique advantages for clinical applications, including fewer islets needed for successful islet transplantation. Competing Interests: EK, NK, and RL are employees of Astellas Institute for Regenerative Medicine, a wholly owned subsidiary of Astellas Pharma engaged in the area of stem cells and regenerative medicine. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Bertera, Knoll, Knoll, Hara, Kimbrel, Kouris, Lanza, Philips, Garciafigueroa, Giannoukakis, Cooper, Trucco and Bottino.)
Databáze:	MEDLINE
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