A Abyzov

AA Mack

C Unger

D Ilic

D Kim

EC Hayden

EC Jonlin

F Jia

G Chen

H Hiura

J Durruthy-Durruthy

J Wang

J Yu

JP Awe

K Rajala

K Takahashi

L Devito

L Warren

M Tong

MJ Martin

N Miyoshi

O Tsuji

P Song

PW Andrews

Q Gu

R Lister

RK Merling

S Abbasalizadeh

S Kriks

SD Schwartz

SM Hussein

X Lian

Abstract
                Introduction
                Human induced pluripotent stem cells (hiPSCs) are considered as one of the most promising seed cell sources in regenerative medicine. Now hiPSC-based clinical trials are underway. To ensure clinical safety, cells used in clinical trials or therapies should be generated under GMP conditions, and with Xeno-free culture media to avoid possible side effects like immune rejection that induced by the Xeno reagents. However, up to now there are no reports for hiPSC lines developed completely under GMP conditions using Xeno-free reagents.
              
                Methods
                Clinical-grade human foreskin fibroblast (HFF) cells used as feeder cells and parental cells of the clinical-grade hiPSCs were isolated from human foreskin tissues and cultured in Xeno-free media. Clinical-grade hiPSCs were derived by integration-free Sendai virus-based reprogramming kit in Xeno-free pluriton™ reprogramming medium or X medium. Neural cells and cardiomyocytes differentiation were conducted following a series of spatial and temporal specific signals induction according to the corresponding lineage development signals. Biological safety evaluation of the clinical-grade HFF cells and hiPSCs were conducted following the guidance of the “Pharmacopoeia of the People's Republic of China, Edition 2010, Volume III”.
              
                Results
                We have successfully derived several integration-free clinical-grade hiPSC lines under GMP-controlled conditions and with Xeno-free reagents culture media in line with the current guidance of international and national evaluation criteria. As for the source of hiPSCs and feeder cells, biological safety evaluation of the HFF cells have been strictly reviewed by the National Institutes for Food and Drug Control (NIFDC). The hiPSC lines are pluripotent and have passed the safety evaluation. Moreover, one of the randomly selected hiPSC lines was capable of differentiating into functional neural cells and cardiomyocytes in Xeno-free culture media.
              
                Conclusion
                The clinical-grade hiPSC lines therefore could be valuable sources for future hiPSC-based clinical trials or therapies and for drug screening.
              </jats:sec

Juan Wang

Jie Hao

Donghui Bai

Qi Gu

Weifang Han

Lei Wang

Yuanqing Tan

Xia Li

Ke Xue

Pencheng Han

Zhengxin Liu

Yundan Jia

Jun Wu

Lei Liu

Liu Wang

Wei Li

Zhonghua Liu

Qi Zhou

Crossref

Stem Cell Research & Therapy

Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions

https://stemcellres.biomedcentral.com/track/pdf/10.1186/s13287-015-0206-y?site=stemcellres.biomedcentral.com

Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions

Abstract

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