Cargando…

Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts

BACKGROUND: Comparing non-inbred autologous and allogeneic induced pluripotent stem cells (iPSCs) and their secreted subcellular products among non-human primates is critical for choosing optimal iPSC products for human clinical trials. METHODS: iPSCs were induced from skin fibroblastic cells of adu...

Descripción completa

Detalles Bibliográficos
Autores principales: Lu, Meng, Peng, Lu, Ming, Xu, Wang, Xiaokai, Cui, Anfeng, Li, Yijun, Wang, Xinhong, Meng, Dan, Sun, Ning, Xiang, Meng, Chen, Sifeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491387/
https://www.ncbi.nlm.nih.gov/pubmed/30926422
http://dx.doi.org/10.1016/j.ebiom.2019.03.011
_version_ 1783414924581535744
author Lu, Meng
Peng, Lu
Ming, Xu
Wang, Xiaokai
Cui, Anfeng
Li, Yijun
Wang, Xinhong
Meng, Dan
Sun, Ning
Xiang, Meng
Chen, Sifeng
author_facet Lu, Meng
Peng, Lu
Ming, Xu
Wang, Xiaokai
Cui, Anfeng
Li, Yijun
Wang, Xinhong
Meng, Dan
Sun, Ning
Xiang, Meng
Chen, Sifeng
author_sort Lu, Meng
collection PubMed
description BACKGROUND: Comparing non-inbred autologous and allogeneic induced pluripotent stem cells (iPSCs) and their secreted subcellular products among non-human primates is critical for choosing optimal iPSC products for human clinical trials. METHODS: iPSCs were induced from skin fibroblastic cells of adult male rhesus macaques belonging to four unrelated consanguineous families. Teratoma generativity, host immune response, and skin wound healing promotion were evaluated subsequently. FINDINGS: All autologous, but no allogeneic, iPSCs formed teratomas, whereas all allogeneic, but no autologous, iPSCs caused lymphocyte infiltration. Macrophages were not detectable in any wound. iPSCs expressed significantly more MAMU A and E of the major histocompatibility complex (MHC) class I but not more other MHC genetic alleles than parental fibroblastic cells. All topically disseminated autologous and allogeneic iPSCs, and their exosomes accelerated skin wound healing, as demonstrated by wound closure, epithelial coverage, collagen deposition, and angiogenesis. Allogeneic iPSCs and their exosomes were less effective and viable than their autologous counterparts. Some iPSCs differentiated into new endothelial cells and all iPSCs lost their pluripotency in 14 days. Exosomes increased cell viability of injured epidermal, endothelial, and fibroblastic cells in vitro. Although exosomes contained some mRNAs of pluripotent factors, they did not impart pluripotency to host cells. INTERPRETATION: Although all of the autologous and allogeneic iPSCs and exosomes accelerated wound healing, allogeneic iPSC exosomes were the preferred choice for “off-the shelf” iPSC products, owing to their mass-production, with no concern of teratoma formation. FUND: National Natural Science Foundation of China and National Key R&D Program of China.
format Online
Article
Text
id pubmed-6491387
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-64913872019-05-06 Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts Lu, Meng Peng, Lu Ming, Xu Wang, Xiaokai Cui, Anfeng Li, Yijun Wang, Xinhong Meng, Dan Sun, Ning Xiang, Meng Chen, Sifeng EBioMedicine Research paper BACKGROUND: Comparing non-inbred autologous and allogeneic induced pluripotent stem cells (iPSCs) and their secreted subcellular products among non-human primates is critical for choosing optimal iPSC products for human clinical trials. METHODS: iPSCs were induced from skin fibroblastic cells of adult male rhesus macaques belonging to four unrelated consanguineous families. Teratoma generativity, host immune response, and skin wound healing promotion were evaluated subsequently. FINDINGS: All autologous, but no allogeneic, iPSCs formed teratomas, whereas all allogeneic, but no autologous, iPSCs caused lymphocyte infiltration. Macrophages were not detectable in any wound. iPSCs expressed significantly more MAMU A and E of the major histocompatibility complex (MHC) class I but not more other MHC genetic alleles than parental fibroblastic cells. All topically disseminated autologous and allogeneic iPSCs, and their exosomes accelerated skin wound healing, as demonstrated by wound closure, epithelial coverage, collagen deposition, and angiogenesis. Allogeneic iPSCs and their exosomes were less effective and viable than their autologous counterparts. Some iPSCs differentiated into new endothelial cells and all iPSCs lost their pluripotency in 14 days. Exosomes increased cell viability of injured epidermal, endothelial, and fibroblastic cells in vitro. Although exosomes contained some mRNAs of pluripotent factors, they did not impart pluripotency to host cells. INTERPRETATION: Although all of the autologous and allogeneic iPSCs and exosomes accelerated wound healing, allogeneic iPSC exosomes were the preferred choice for “off-the shelf” iPSC products, owing to their mass-production, with no concern of teratoma formation. FUND: National Natural Science Foundation of China and National Key R&D Program of China. Elsevier 2019-03-26 /pmc/articles/PMC6491387/ /pubmed/30926422 http://dx.doi.org/10.1016/j.ebiom.2019.03.011 Text en © 2019 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research paper
Lu, Meng
Peng, Lu
Ming, Xu
Wang, Xiaokai
Cui, Anfeng
Li, Yijun
Wang, Xinhong
Meng, Dan
Sun, Ning
Xiang, Meng
Chen, Sifeng
Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title_full Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title_fullStr Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title_full_unstemmed Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title_short Enhanced wound healing promotion by immune response-free monkey autologous iPSCs and exosomes vs. their allogeneic counterparts
title_sort enhanced wound healing promotion by immune response-free monkey autologous ipscs and exosomes vs. their allogeneic counterparts
topic Research paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491387/
https://www.ncbi.nlm.nih.gov/pubmed/30926422
http://dx.doi.org/10.1016/j.ebiom.2019.03.011
work_keys_str_mv AT lumeng enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT penglu enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT mingxu enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT wangxiaokai enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT cuianfeng enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT liyijun enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT wangxinhong enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT mengdan enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT sunning enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT xiangmeng enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts
AT chensifeng enhancedwoundhealingpromotionbyimmuneresponsefreemonkeyautologousipscsandexosomesvstheirallogeneiccounterparts