scholarly journals Challenges in the clinical application of induced pluripotent stem cells

10.1186/scrt9 ◽  
2010 ◽  
Vol 1 (1) ◽  
pp. 9 ◽  
Author(s):  
Douglas Sipp
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Induced Pluripotent

Large Animal Models for the Clinical Application of Human Induced Pluripotent Stem Cells

2019 ◽  
Vol 28 (19) ◽  
pp. 1288-1298 ◽  
Author(s):  
Xiaoqiang Cong ◽  
Shang-Min Zhang ◽  
Matthew W. Ellis ◽  
Jiesi Luo
Keyword(s):  
Stem Cells ◽  
Animal Models ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Large Animal ◽  
Large Animal Models ◽  
Induced Pluripotent

Clinical Application of Induced Pluripotent Stem Cells in Cardiovascular Medicine

Cardiology ◽  
2015 ◽  
Vol 131 (4) ◽  
pp. 236-244 ◽  
Author(s):  
Hong-jie Chi ◽  
Song Gao ◽  
Xin-chun Yang ◽  
Jun Cai ◽  
Wen-shu Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Drug Screening ◽  
Pluripotent Stem Cells ◽  
Disease Diagnosis ◽  
The Body ◽  
Patient Specific ◽  
Human Ipscs ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.

Efficient Induction of CD34+ Progenitor Cells From Human Bone Marrow Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells with Defined Chemicals

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2347-2347
Author(s):  
Yulin Xu ◽  
Lizhen Liu ◽  
Shan Fu ◽  
Lifei Zhang ◽  
Yongxian Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Endothelial Cell ◽  
Induced Pluripotent Stem Cells ◽  
Progenitor Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
Cell Potential ◽  
Efficient Induction ◽  
Induced Pluripotent

Abstract Abstract 2347 Induced pluripotent stem cells (iPSCs) hold great potential in clinical application with indefinite passages, pluripotency of forming three germ layers and immunological compatibility with patients. Human bone marrow mesenchymal stem cell-derived iPSCs (hBMMSC-iPSCs) may have more virtues than other types of cell–derived iPSCs do in diseases treatment for their wide application in clinic for many years. Efficient differentiation of induced pluripotent stem cells (iPSCs) to a specialized cell type is a crucial step for iPSC clinical application. CD34+ progenitor cells derived from hBMMSC-iPSCs by treatment with defined chemicals have not been reported. Here, base on the efficient generation of hBMMSC-iPSCs with cDNA encoding four transcription factors OCT4, SOX2, KLF4 and c-MYC, and the compounds of p53 siRNA, VPA and Vc, we proposed that CD34+ progenitor cells, retaining hematopoietic and endothelial cell potential, could be efficiently obtained from hBMMSC-iPSCs by treatments with chemicals exerting function on mesoderm and hematopoietic cells. The differentiated hBMMSC-iPSCs treated with the chemicals comprised nearly 20% proportion of CD34+ progenitor cells, about 20-fold increasing compared to the spontaneous differentiation hBMMSC-iPSCs and higher than that from human skin fibroblast-derived iPSCs (hFib-iPSCs) (nearly 15%) and human embryonic stem cell line H1 (nearly 17%) by flow cytometry analysis. Those cells retained the hematopoietic and endothelial cell potential as CD34+ progenitor cells derived from umbilical cord blood. After coculture with the first chemical cocktails including BMP4 and SCF for 5 days, a higher proportion of the mesoderm cells were induced from hBMMSC-iPSCs than that from the untreated groups (P<0.05) by analysis the expression of Brachyury and GATA2 with RT-PCR and immunochemistry analysis. The efficient mesoderm cell activity was then directed to CD34+ progenitor cells with the following chemicals as SCF and IL-3 for another 7–9 days by analysis of cellular phenotype and the expression of the hematopoietic transcription factors TAL-1 and GATA-2. Sorted by CD34 magnetic separation and exposed to semisolid media with the hematopoietic cytokines including EPO and G-CSF, CD34+ progenitor cells formed various hematopoietic colonies as BFU-E, CFU-E, CFU-G, CFU-GM, and CFU-GEMM. CFUs derived from hBMMSC-iPSC groups treated with the chemicals outnumbered those from hFib-iPSCs, the spontaneous differentiation hBMMSC-iPSCs and H1 groups. Hematopoietic cell lineages as erythroid, granulocyte, and megakaryocyte were identified with Wright-Giemsa staining. During the hematopoietic commitment of hBMMSC-iPSCs, the pluripotent gene Oct4 continued to be down-regulated and completely vanished at day 14 after the induction. However, the expression of the hematologic transcription factor GATA-2 experienced a dynamic process with up-regulation at the initial induction stage and then gradual down-regulation after CD34+ progenitor cell commitment to CFU forming. Endothelial cell potential of CD34+ progenitor cells was also verified by demonstration of the vascular tube-like structure formation and the expression of endothelial specific markers CD31 and VE-CADHERIN. The efficient induction of CD34+ progenitor cells from hBMMSC-iPSCs with defined chemicals, avoiding contamination from indentified factors with using mouse feeder lays or other poorly defined induction components, gives an opportunity for the generation of unlimited HLA matched transplantable cells, provides cell models for study the mechanism of haemopoiesis and related diseases, and therefore promotes iPSC clinical application. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Standards of induced pluripotent stem cells derived clinical-grade neural stem cells preparation and quality control (2021 China version)

2021 ◽  
Vol 9 (1) ◽  
pp. 13-30
Author(s):  
Meng Cai ◽  
Fabin Han ◽  
Nanxiang Xiong ◽  
Yihao Wang ◽  
Shiqing Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Clinical Application ◽  
Pluripotent Stem Cells ◽  
International Association ◽  
Embryonic Stem ◽  
Biological Properties ◽  
Human Virus ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) have become the leading research object in the clinical application of restorative medicine. They are easily generated from diverse cell sources and functionally indistinguishable from embryonic stem cells without the accompanying ethical issues. To date, the use of iPSC-derived neural stem cells and their progeny in the treatment of neurodegenerative and injurious diseases has achieved good results, with great potential in cell drug development. However, because of some unique biological properties and differences from traditional drug production processes, cell drug research and development has many problems that can hinder clinical applications. Given this situation, the Chinese Association of Neurorestoratology (Preparatory) and China Committee of the International Association of Neurorestoratology have organized relevant professional experts to formulate the standard presented here. Overall, the aim was to promote the clinical application of neural stem cells (NSCs) and their further derived neural cells from iPSC sources and promote cell drugs’ production and development. This standard refers to the latest research results, quality evaluation criteria for traditional medicines, and the regulatory framework for cellular treatments. The standard considers general biological properties of cells, including cell morphology, cell cycle, karyotype, and cell viability. The specific biological properties of NSCs, such as cell surface markers and differentiation ability, general drug standards, such as aseptic testing, endotoxins, human virus detection, and cell-related drug standards, such as telomerase activity and tumorigenicity, are also considered. This standard will serve as a reference for physicians and scientists who focus on clinical nervous cell applications and studies related to iPSCs.

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