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-9 Microcapsules in melt electrowritten scaffolds as a delivery device for human pluripotent stem cell derived islets

Bernard Tuch, Australia

Australian Foundation for Diabetes Research
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Australian Foundation for Diabetes Research


Microcapsules in melt electrowritten scaffolds as a delivery device for human pluripotent stem cell derived islets

BERNARD TUCH1,2, Iris Cheng3, Tim Dargaville4, Kfir Molakandov5, Alon Levy5, Hui Chen3, Michel Revel5.

1Australian Foundation for Diabetes Research, Sydney, Australia; 2Diabetes, Central Clinical School, Monash University, Melbourne, Australia; 3School of Life Sciences, University of Technology Sydney, Sydney, Australia; 4School of Chemistry & Physics, Queensland University of Technology, Brisbane, Australia; 5Kadimastem Ltd, Nes Ziona, Israel


Human pluripotent stem cell derived islets, like pancreatic islets, normalise blood glucose levels (BGL) of diabetic rodent recipients.  However, to be of practical assistance to diabetic humans, the cells need to be delivered without systemic immunosuppression.  Placing the islets in alginate microcapsules provides immuno-isolation, but to be retrievable as is required by regulatory bodies, the capsules need to be placed in a single device.  


We tested the functional capacity of pancreatic and stem cell derived islets that were microencapsulated and placed in melt electrowritten scaffolds made of polycaprolactone, implanted either subcutaneously (sc) or intraperitoneally (ip) in diabetic mice. The human islets were derived from human embryonic stem cells over a period of 28 days1


Microencapsulated QS mouse pancreatic islets placed in a prevascularised tubular scaffold rapidly normalised BGL of diabetic BALB/c mice (800-1000 islets/mouse) and maintained values of <12 mmol/L for 60-105 days2.  Microencapsulated human stem cell derived islets (SI) placed in tubular scaffolds and implanted sc or ip in diabetic NOD/SCID mice (3500 islets/mouse) also normalised BGL but 3 weeks later the mice became hyperglycaemic again and remained so thereafter.  This was in the presence of increasing levels of human C-peptide: 16 pmol/L at 2 weeks (sc/ip); 42 pmol/L at 5 weeks (sc/ip); 31 (sc) & 92 pmol/L (ip) at 10 weeks.  Histological analysis of the graft at 93 days showed viable islets with good vascularisation but partial infiltration of the scaffold with fibrous tissue.  By contrast, encapsulated SI (3500/mouse) infused directly into the peritoneal cavity of diabetic NOD/SCID mice rapidly achieved normoglycaemia and maintained these levels for the 3 month experimental duration.  C-peptide levels at 2, 5 and 10 weeks post-transplant were 167, 197 and 261 pmol/L, respectively, levels higher than those in mice implanted with encapsulated SI scaffolds. An ip glucose tolerance test was normal with basal BGL of 4.9 mmol/L, peak values of 13.2 mmol/L at 15 min, and return to basal levels by 60 minutes. 


Microencapsulated SI  normalise BGL of diabetic mice for at least 3 months.  Placing the encapsulated islets in tubular scaffolds does not inhibit the survival of the tissue but does result in the secretion of a lesser amount of insulin, possibly because of an unfavourable milieu for the ß cells. 

National Stem Cell Foundation of Australia. New South Wales and Israeli Governments.


[1] Molakandov K, Berti DA, Beck A, Elhanani O, Walker MD, Soen Y, Yavriyants K, Zimerman M, Volman E, Toledo I, Erukhimovich A, Levy AM, Hasson A, Itskovitz-Eldor J, Chebath J, Revel M. Selection for CD26- and CD49A+ Cells from pluripotent stem cells-derived islet-like clusters improves therapeutic activity in diabetic mice. Front Endocrinol 2021; 12: 635405
[2] Mridha, AR, Dargaville TR, Dalton PD, Carroll L, Morris MB, Vijayaganapathy V, Tuch BE. Prevascularized retrievable hybrid implant to enhance function of subcutaneous encapsulated islets. Tissue Eng Part A 2022; 28: 212-24

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