Methods and compositions for treatment of type 1 diabetes using fibroblasts as facilitators of islet engraftment
Embodiments of the disclosure pertain to the treatment of diabetes through replacement of insulin producing cells. In specific embodiments, the disclosure encompasses the use of cellular adjuvants to enhance survival, engraftment and tolerogenesis of insulin-producing cells. In certain cases the disclosure concerns the manipulation of a hepatic microenvironment to promote immunological tolerance at an enhanced level to allow for integration of allogeneic insulin-producing cells. Particular embodiments utilize fibroblasts to enhance immunological tolerance for insulin-producing cells upon engraftment.
1 . A method of enhancing survival of allogeneic or autologous insulin-producing cells in an individual, comprising the steps of administering a composition comprising an effective amount of fibroblasts prior to, concurrent with, and/or subsequent to transplantation of said allogeneic or autologous insulin-producing cells in the individual; wherein said fibroblasts are CD73-positive.
2 . The method of claim 1 , wherein the fibroblasts are allogeneic to the individual.
3 . The method of claim 1 , wherein the allogeneic insulin-producing cells are derived from a pancreatic donor.
4 . The method of claim 1 , wherein the allogeneic insulin-producing cells are comprised of islet cell mass.
5 . The method of claim 1 , wherein said allogeneic insulin producing cells are derived from in vitro differentiation from a population of progenitor cells.
6 . The method of claim 1 , wherein the composition further comprises endothelial progenitor cells (EPCs).
7 . The method of claim 6 , wherein said EPCs express markers selected from the group consisting of: a) flk-1; b) CD31; c) CD34; d) CD133; f) PDGF-R; g) hTERT; and h) a combination thereof.
8 . The method of claim 6 , wherein the EPCs are derived by a method comprising the steps of: (i) isolating a mammalian cellular population; (ii) enriching for a subpopulation of the cells of step (i) that expresses a CD45 phenotypic profile; (iii) enriching for a subpopulation of the CD45 − cells derived from step (ii) that express a CD34 + phenotypic profile; and (iv) isolating the subpopulation of CD34 + cells derived from step (iii) that express a CD31 lo/− phenotypic profile, to thereby isolate the endothelial progenitor cells.
9 . The method of claim 6 , wherein the EPCs are derived from placental tissue, bone marrow, adipose tissue, omentum, or a combination thereof.