Short-term glycemic improvement by co-transplantation of human amniotic epithelial cells and allogeneic islets in a diabetic rat model
Kaoru Okada1, Kazuaki Tokodai1, Hitomi Okita2, Manami Yoshida2, Asami Sasaki2, Takako Ito2, Tetsuro Hoshiai3, Masatoshi Saito4, Toshio Miki5, Masafumi Goto2,6, Takashi Kamei1.
1Department of Surgery, Tohoku University, Sendai, Japan; 2Transplantation and Regenerative Medicine Center, Tohoku University Hospital, Sendai, Japan; 3Department of Obstetrics and Gynecology, Tohoku University, Sendai, Japan; 4Department of Maternal and Fetal Therapeutics, Tohoku University, Sendai, Japan; 5Department of Physiology, Nihon University, Tokyo, Japan; 6Division of Transplantation and Regenerative Medicine, Tohoku University School of Medicine, Sendai, Japan
Introduction:
Islet transplantation is a minimally invasive therapy for type 1 diabetes mellitus. However, early graft loss remains a critical barrier, limiting the success of single-donor transplantation. Co-transplantation with stem cells has emerged as a promising approach to enhance islet engraftment. Human amniotic epithelial cells (hAECs), a type of perinatal stem cell, possess angiogenic, anti-inflammatory, and immunomodulatory properties, making them a potential supportive cell source. This study aimed to evaluate whether co-transplantation of hAECs with islets could improve islet engraftment in a diabetic rat model.
Methods:
Human amniotic membranes (hAMs) were collected from term placentas after elective cesarean section, with informed consent. hAECs were isolated and cryopreserved in liquid nitrogen.
Diabetes was induced in Lewis rats using streptozotocin 7–8 days prior to transplantation. A total of 4,000 IEQs of allogeneic islets from Wistar-ST rats were transplanted via the portal vein, either alone (control group) or mixed with 1.0×10⁶ hAECs (Co-Tx group). Blood glucose levels were monitored post-transplantation. Serum samples were collected in the early post-transplant period, and inflammatory cytokines were quantified using a multiplex assay.
Results:
The Co-Tx group exhibited a significantly longer duration of normoglycemia compared to the control group (p = 0.05). However, blood glucose levels gradually increased in both groups over time, and long-term islet function was not sustained.
Cytokine analysis revealed significantly lower serum levels of C-X-C motif chemokine ligand 1 (CXCL1) in the Co-Tx group compared to controls (p = 0.015).
Conclusions:
Co-transplantation of hAECs with allogeneic islets improved short-term glycemic control in diabetic rats, potentially via suppression of CXCL1-mediated inflammation. These findings suggest that hAECs may modulate early inflammatory responses after islet transplantation. Further studies are warranted to optimize this strategy and promote long-term islet engraftment.
Japan Society for the Promotion of Science (JSPS KAKENHI) Grant Number: 22K08745.
References:
[1] human amniotic epithelial cell
[2] stem cell
[3] islet transplantation
Lectures by Kaoru Okada
| When | Session | Talk Title | Room |
|---|---|---|---|
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Thu-23 18:30 - 19:30 |
Poster Session | Short-term glycemic improvement by co-transplantation of human amniotic epithelial cells and allogeneic islets in a diabetic rat model |