Comparison of fetal porcine aggregates of purified beta-cells versus islet-like cell clusters as a treatment of diabetes.
Fetal pig islet-like cell clusters (ICCs) have the potential to reverse diabetes 1-5 months after transplantation. In a fetal ICC, however, beta-cells constitute only 6-8% of the cells, in contrast to 65% in an adult pig islet. Attempts to purify fetal beta-cells from cell clusters and compare their function to that of ICCs have not been shown previously. Beta-cells were purified from ICCs isolated from the fetal pig pancreas. These were then aggregated and maintained in culture for 3 days. ICCs were isolated from fetal pig pancreas and allowed to round up in culture for 3 days. Transplantation of aggregates and ICCs (10,000 and 12,600, respectively) into diabetic immunoincompetent mice resulted in normoglycemia at 18 +/- 2 and 8 +/- 1 weeks, respectively (p = 0.0006). Removal of grafts after normalization of blood glucose levels resulted in rapid return of hyperglycemia in both groups. In conclusion, a purified population of immature beta-cells can be produced from the fetal pig pancreas. The reason these cells take longer than ICCs to reverse diabetes when transplanted is postulated to be because of the relative lack of precursor cells from which beta-cells differentiate. This finding may have implications for stem cell therapy, as other cell types, other than purified beta-cells, may be necessary for appropriate function in vivo.
Tu
Jian
J
Diabetes Transplant Unit, The Prince of Wales Hospital, The University of New South Wales, Sydney, NSW 2031, Australia.
Khoury
Pauline
P
Williams
Lindy
L
Tuch
Bernard E
BE
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D016332:Fetal Tissue Transplantation / Q000379:methods; D005941:Glucokinase / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D010179:Pancreas / Q000196:embryology; D013552:Swine; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005941:Glucokinase