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胚胎猪胰腺组织移植治疗糖尿病。

Embryonic pig pancreatic tissue transplantation for the treatment of diabetes.

作者信息

Eventov-Friedman Smadar, Tchorsh Dalit, Katchman Helena, Shezen Elias, Aronovich Anna, Hecht Gil, Dekel Benjamin, Rechavi Gideon, Blazar Bruce R, Feine Ilan, Tal Orna, Freud Enrique, Reisner Yair

机构信息

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.

出版信息

PLoS Med. 2006 Jul;3(7):e215. doi: 10.1371/journal.pmed.0030215.

DOI:10.1371/journal.pmed.0030215
PMID:16768546
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1479387/
Abstract

BACKGROUND

Transplantation of embryonic pig pancreatic tissue as a source of insulin has been suggested for the cure of diabetes. However, previous limited clinical trials failed in their attempts to treat diabetic patients by transplantation of advanced gestational age porcine embryonic pancreas. In the present study we examined growth potential, functionality, and immunogenicity of pig embryonic pancreatic tissue harvested at different gestational ages.

METHODS AND FINDINGS

Implantation of embryonic pig pancreatic tissues of different gestational ages in SCID mice reveals that embryonic day 42 (E42) pig pancreas can enable a massive growth of pig islets for prolonged periods and restore normoglycemia in diabetic mice. Furthermore, both direct and indirect T cell rejection responses to the xenogeneic tissue demonstrated that E42 tissue, in comparison to E56 or later embryonic tissues, exhibits markedly reduced immunogenicity. Finally, fully immunocompetent diabetic mice grafted with the E42 pig pancreatic tissue and treated with an immunosuppression protocol comprising CTLA4-Ig and anti-CD40 ligand (anti-CD40L) attained normal blood glucose levels, eliminating the need for insulin.

CONCLUSIONS

These results emphasize the importance of selecting embryonic tissue of the correct gestational age for optimal growth and function and for reduced immunogenicity, and provide a proof of principle for the therapeutic potential of E42 embryonic pig pancreatic tissue transplantation in diabetes.

摘要

背景

有人提出移植胚胎猪胰腺组织作为胰岛素来源以治疗糖尿病。然而，先前有限的临床试验未能通过移植孕晚期猪胚胎胰腺来治疗糖尿病患者。在本研究中，我们检测了不同胎龄获取的猪胚胎胰腺组织的生长潜力、功能及免疫原性。

方法与结果

将不同胎龄的猪胚胎胰腺组织植入重症联合免疫缺陷（SCID）小鼠体内，结果显示胚胎第42天（E42）的猪胰腺能使猪胰岛大量生长并持续较长时间，还能使糖尿病小鼠恢复正常血糖水平。此外，对异种组织的直接和间接T细胞排斥反应均表明，与E56或更晚胚胎期的组织相比，E42组织的免疫原性显著降低。最后，用包含细胞毒性T淋巴细胞相关抗原4免疫球蛋白（CTLA4-Ig）和抗CD40配体（抗CD40L）的免疫抑制方案治疗的、移植了E42猪胰腺组织的完全免疫活性糖尿病小鼠血糖水平恢复正常，不再需要胰岛素。

结论

这些结果强调了选择正确胎龄的胚胎组织对于实现最佳生长和功能以及降低免疫原性的重要性，并为E42猪胚胎胰腺组织移植治疗糖尿病的潜在疗效提供了原理证明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/ca390f47bba0/pmed.0030215.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/77533525db8d/pmed.0030215.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/313ca5ec27d4/pmed.0030215.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/296b9b0f87d0/pmed.0030215.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/b8a0f06fa7fc/pmed.0030215.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/15226f8e7a26/pmed.0030215.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/bc9bd6d2a4b5/pmed.0030215.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/ca390f47bba0/pmed.0030215.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/77533525db8d/pmed.0030215.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/313ca5ec27d4/pmed.0030215.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/296b9b0f87d0/pmed.0030215.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/b8a0f06fa7fc/pmed.0030215.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/15226f8e7a26/pmed.0030215.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/bc9bd6d2a4b5/pmed.0030215.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5deb/1518700/ca390f47bba0/pmed.0030215.g007.jpg

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