We aimed to blunt islet β-cell directed autoimmune aggression as a potential approach for the treatment of Type 1 Diabetes (T1D). For this purpose, we proposed the use of a particular type of Mesenchymal Stem Cells, retrieved from the post-partum umbilical cord Wharton Jelly (hUCMS). To maximize hUCMS immunomodulatory potential, that has been proven impaired by cell-to-cell contact, we encapsulated these cells within highly purified, alginate-based microcapsules. Encapsulation enabled physical isolation of the cells from the host’s immune system. Pilot in vitro experiments where microencapsulated hUCMS were co-incubated with PBMCs derived from T1D patients showed induction of Treg and rebalance of Th1/Th2 cells. In vivo studies in diabetic NOD mice showed that microencapsulated hUCMS yield long-term remission of hyperglycemia. Use of the encapsulated hUCMS showed that in cell-based immunomodulatory strategies, the transplanted cells can benefit from encapsulation. It is likely that such immune-therapeutic approach could have efficacy only if residual native β-cell mass is still present. Otherwise, hUCMS-induced rehabilitation of the immune system would be unable to grant for reversal of diabetes. The proposed method, employing hUCMS in alginate microcapsules, presents a good safety and efficacy profile. This could warrant initiation of pilot human clinical trials of microencapsulated hUCMS grafts patients with recent-onset T1D.
Microencapsulated Umbilical Cord Wharton Jelly-Derived Human Mesenchymal Stem Cells for the Cell Therapy of Type 1 Diabetes Mellitus (T1d): Applications and Limits
Montanucci P.;Pescara T.;Basta G.;Calafiore R.
2017
Abstract
We aimed to blunt islet β-cell directed autoimmune aggression as a potential approach for the treatment of Type 1 Diabetes (T1D). For this purpose, we proposed the use of a particular type of Mesenchymal Stem Cells, retrieved from the post-partum umbilical cord Wharton Jelly (hUCMS). To maximize hUCMS immunomodulatory potential, that has been proven impaired by cell-to-cell contact, we encapsulated these cells within highly purified, alginate-based microcapsules. Encapsulation enabled physical isolation of the cells from the host’s immune system. Pilot in vitro experiments where microencapsulated hUCMS were co-incubated with PBMCs derived from T1D patients showed induction of Treg and rebalance of Th1/Th2 cells. In vivo studies in diabetic NOD mice showed that microencapsulated hUCMS yield long-term remission of hyperglycemia. Use of the encapsulated hUCMS showed that in cell-based immunomodulatory strategies, the transplanted cells can benefit from encapsulation. It is likely that such immune-therapeutic approach could have efficacy only if residual native β-cell mass is still present. Otherwise, hUCMS-induced rehabilitation of the immune system would be unable to grant for reversal of diabetes. The proposed method, employing hUCMS in alginate microcapsules, presents a good safety and efficacy profile. This could warrant initiation of pilot human clinical trials of microencapsulated hUCMS grafts patients with recent-onset T1D.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
