Session Time: 3:15pm-4:45pm
Presentation Time: 3:39pm-3:51pm
*Purpose: Islet transplantation is one of the most promising hopes for a cure for type 1 diabetes, although islet shortage remains a serious concern. A possible solution is to generate cells from non-islet sources (stem cells) for replacement therapy; however, current techniques are labor-intensive, require multiple steps, a myriad of factors, many weeks to obtain the desired cells, which in some cases are oncogenic, and can be very costly. We recently developed a novel cell population, AIPCs (Activated Islet Proliferating Cells), from isolated human islets using a simple culture protocol that can generate billions of insulin-producing islet cells.
*Methods: IMG-i is a reagent with a proprietary peptide that induces islet cells to mobilize and proliferate. These cells are over 65% CD133-, Ki67- and insulin-triple-positive. AIPCs are over 70% double-positive for both insulin and glucagon and can secrete both hormones when stimulated with various secretagogues. AIPCs can be cultured and expanded in vitro for long periods of time (over 200 days) and maintain their marker profile and ability to respond to physiological stimuli. When allowed to grow to confluency, AIPCs form Dithizone-positive islet-like cell clusters that respond to glucose stimulation and putatively represent de novo islets. To assess the ability of AIPCs to engraft and survive in a hyperglycemic environment, produce insulin, and avoid transformation, AIPCs (a bolus of 4 million) were transplanted under the kidney capsule of STZ-diabetic mice (n=6).
*Results: Within 14 days post-implantation, human insulin was detected in the serum; by day 56, all implanted animals were secreting human insulin until elective termination of the study after 100 days. Histological analysis of the implanted areas of the kidney capsule displayed no tumor formation and the presence of insulin-positive, islet-like formations.
*Conclusions: We present a simple culture protocol that allows the mobilization and long-term culture of insulin and glucagon-expressing islet derived cells. These cells do not display any tumorigenic effects in vivo in mice and can be transplanted without any modification or alteration. If the observed propagation rates of AIPCs are confirmed in a broader pool of islet donors, it is estimated that isolated islets from a single donor pancreas could generate 20 billion AIPCs within four weeks, which should be sufficient to treat multiple patients. AIPCs represent not only a novel cell population and tool to further study islet cell biology, but a realistic cellular approach for the treatment of diabetes.
To cite this abstract in AMA style:Pollett JB, Bottino R, Bertera S, Trucco M, Thai N. Generation and Long-Term Culturing of AIPCs for Islet Replacement [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/generation-and-long-term-culturing-of-aipcs-for-islet-replacement/. Accessed September 22, 2020.
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