Remission of hyperglycemia in spontaneously diabetic NOD mice upon transplant of microencapsulated human umbilical cord Wharton jelly‐derived mesenchymal stem cells (hUCMS)

Abstract

Background: Our previous in vitro demonstration of the immunoregulatory effects of microencapsulated hUCMS on human peripheral blood mononuclear cells (PBMCs) extracted from patients with recent onset, type 1 diabetes mellitus (DM), prompted us to test our product for xenograft (TX) in non obese diabetic (NOD) mice with spontaneous DM. Methods:We transplanted microencapsulated hUCMS into the peritoneal cavity of NOD mice with either severe or mild DM. Blood glucose (BG) levels were monitored following TX, in either basal or upon glucose stimulation. Results:Only the NODs with mild DM showed full and sustained remission of hyperglycemia throughout 216 days post-TX, unlike recipients with severe DM, where no remission of hyperglycemia was attained, as reflected by erratic BG levels at all times. Conclusions:These data suggest that the stage of DM disease process in NOD mice, reflecting steady decline of residual b-cell mass, plays a pivotal role in determining the success of this cell therapy approach for treatment of DM. K E Y W O R D Simmunoregulation, microencapsulation, NOD mice, sodium alginate, stem cells, T1D

Co‐microencapsulation of human umbilical cord‐derived mesenchymal stem and pancreatic islet‐derived insulin producing cells in experimental type 1 diabetes

“…The microcapsules fully protected the grafted tissue from the host's immune system. We had shown that T1D treatment with hUCMS alone worked only within a certain time frame of the disease process initiation, 28 anyway early enough, when still congruous β‐cell mass was present. On the contrary, the hUMSC/hIDC co‐aggregate, by securing a certain amount of insulin secretion, would be effective also with residual β‐cells function.…”

“…We had preliminarily shown that microencapsulated hUCMS grafts restored euglycemia in non‐obese diabetic (NOD) mice with recent onset, but not long‐standing, T1D, indicating that this cellular system is active only at early stages of the T1D disease process 28 …”

Xenotransplantation literature update, March/April 2019

“…On the other hand, Montanucci et al transplanted microencapsulated human umbilical cord Wharton jelly‐derived mesenchymal stem cells (hUCMS) into the peritoneal cavity of NOD mice with either severe or mild DM . Blood glucose (BG) levels were monitored following xenograft, in either basal or upon glucose stimulation.…”

“…Thus, remission of the disease was achieved only when residual β‐cell mass is present, highlighting the role of intervention in determining the success of treatment. In addition, they reported that the microencapsulated hUCMS, following overnight incubation with IFN‐γ, significantly increased the expression of molecules, associated with immunomodulatory properties, such as indoleamine‐pyrrole 2,3‐dioxygenase (IDO1), and HLA‐G5 . The authors work suggests that is worth mentioning that this type of procedure does not require pre‐graft immunosuppression, and it allows cell xenograft to function, with no rejection events.…”

Experimental models of type 1 diabetes

“…В некоторых случаях такие гены, как Ag7, или такие локусы, как CTLA, рассматриваются в качестве гомологичных у людей и мышей, что позволяет использовать данную модель, в том числе и с помощью трансгенных под ходов, как основу для изучения факторов, ускоряющих или замедляющих развитие СД1 [18,19]. Существует большое количество ра бот, доказывающих эффек тивность таргетной терапии для профилактики и лечения СД1 на данной модели животных [20][21][22]. Однако клинические исследования в полной мере этих выводов не подтверждают.…”