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Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

Forbes, Shareen ; Bond, Andrew R ; Thirlwell, Kayleigh L ; Burgoyne, Paul ; Samuel, Kay ; Noble, June ; Borthwick, Gary ; Colligan, David ; McGowan, Neil W A ; Lewis, Philip Starkey ; Fraser, Alasdair R ; Mountford, Joanne C ; Carter, Roderick N ; Morton, Nicholas M ; Turner, Marc L ; Graham, Gerard J ; Campbell, John D M

Science translational medicine, 2020-01, Vol.12 (526) [Periódico revisado por pares]

United States: The American Association for the Advancement of Science

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Título:
Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization
Autor: Forbes, Shareen ; Bond, Andrew R ; Thirlwell, Kayleigh L ; Burgoyne, Paul ; Samuel, Kay ; Noble, June ; Borthwick, Gary ; Colligan, David ; McGowan, Neil W A ; Lewis, Philip Starkey ; Fraser, Alasdair R ; Mountford, Joanne C ; Carter, Roderick N ; Morton, Nicholas M ; Turner, Marc L ; Graham, Gerard J ; Campbell, John D M
Assuntos: Allografts ; Animals ; Blood Glucose - metabolism ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - surgery ; Graft rejection ; Humans ; Immunodeficiency ; Islet cells ; Islets of Langerhans - metabolism ; Islets of Langerhans Transplantation - methods ; Kidneys ; Lymphocytes T ; Mesenchyme ; Mice ; Pancreas transplantation ; Pancreatic islet transplantation ; Phenotypes ; Portal vein ; Portal Vein - metabolism ; Stromal cells ; Syngeneic grafts ; Umbilical cord ; Umbilical Cord - cytology ; Vascularization
É parte de: Science translational medicine, 2020-01, Vol.12 (526)
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes.
Editor: United States: The American Association for the Advancement of Science
Idioma: Inglês

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Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

United States: The American Association for the Advancement of Science

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