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Stem Cell Res Ther. 2018 Jan 22;9(1):14. doi: 10.1186/s13287-018-0769-5.

Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates.

Author information

1
Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215126, China.
2
Biopharmagen Corp., Suzhou, 215126, China.
3
West China Hospital, University of Sichuan, Chengdu, 610041, China.
4
School of Public Health, University at Albany, Albany, NY, 12201, USA.
5
Department of Pathology, University Hospital, Stony Brook University, Stony Brook, NY, 11794, USA.
6
Biopharmaceutical R&D Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou, 215126, China. yjiang@biopharmagen.com.
7
Biopharmagen Corp., Suzhou, 215126, China. yjiang@biopharmagen.com.

Abstract

BACKGROUND:

Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34+ cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34+ cells for the therapeutic potential of autologous transplantation.

METHODS:

The human and nonhuman primate EPCs from mobilized PB CD34+ cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury.

RESULTS:

The mobilized PB CD34+ cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 108 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 106 ± 3.39 × 105 CD34+ cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs.

CONCLUSIONS:

We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34+ cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that it may be possible for these ex-vivo high-efficient expanded EPCs to be used in clinical cell therapy.

KEYWORDS:

Endothelial progenitor cells; Hepatic sinusoidal endothelium injury; Mobilized peripheral blood; Nonhuman primates

PMID:
29357928
PMCID:
PMC5778763
DOI:
10.1186/s13287-018-0769-5
[Indexed for MEDLINE]
Free PMC Article

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