Concise Review: One Stone for Multiple Birds: Generating Universally Compatible Human Embryonic Stem Cells

Zheng, Dejin; Wang, Xiaofang; Xu, Ren‐He

doi:10.1002/stem.2407

Cited by 36 publications

(29 citation statements)

References 55 publications

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“…Some of the current methods for CM purification still have concerns including inadvertent gene editing, possibly causing misreading and deletions that could further change the phenotype of derived‐CMs and increase the heterogeneity of the cell population. By using a precisely inserted locus like AAVS1, a stable cell line can be established after long‐term selection . Then, efficiency of CM differentiation and reproducibility can be increased.…”

Section: Remaining Challenges Of Using Pscs For MI Therapymentioning

confidence: 99%

“…Though the study was performed on a small number of animals, their results demonstrate the promise of the MHC match system for use in preclinical trials. To overcome immune rejection after transplantation, gene editing has also emerged as a powerful tool to knock out immune receptors such as B2M, CIITA, and MHCII . It is also suggested that administration of MSCs along with PSC‐CMs may confer an immune suppressive effect due to the MSCs that can decrease the T and B cell activation.…”

Section: Remaining Challenges Of Using Pscs For MI Therapymentioning

confidence: 99%

“…By using a precisely inserted locus like AAVS1, a stable cell line can be established after long-term selection. [211] Then, efficiency of CM differentiation and reproducibility can be increased. Purification can also cause ≈10% loss of CMs even with the optimal dosage of agents.…”

Section: Purification Of Psc-derived Cms For MI Therapymentioning

confidence: 99%

“…[225] In addition, tumorigenesis may be avoided by adding inducible suicide cassette PGK-Puro-ΔTK-PA in the genome to induce cell apoptosis when the cells become overly proliferative in vivo. [211] Wang et al reported a similar strategy which incorporated a chemically induced iCas9 system in the genome to remove the unwanted cells after transplantation of hESC-derived MSCs in a wound-healing mouse model. [229] There is also concern on whether this strategy can be rapidly translated into clinic because genome editing may cause unwanted genetic variations, including DNA sequence loss and epigenetic changes to the biological phenotypes of the resultant cells.…”

Section: Tumorigenesis Associated With Psc-derived Cms For MI Therapymentioning

confidence: 99%

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Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Jiang

Shamul

et al. 2020

Advanced Therapeutics

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Myocardial infarction (MI) is a life‐threatening disease resulting from the irreversible death of cardiomyocytes (CMs). Stem cell‐based therapies have been studied for MI treatment over the last two decades with promising outcomes. Here, the past work in this field is critically reviewed to elucidate the advantages and disadvantages of treating MI using pluripotent stem cells (PSCs) including both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), adult stem cells, and cardiac progenitor cells. Overall, PSCs (particularly iPSCs) have more advantages than the other cells for cardiac regeneration. However, the use of iPSCs is also facing critical challenges, which may be resolved by using biomaterials to engineer stem cells for reduced immunogenicity, improved immobilization/survival in the heart, and increased integration with the host cardiac tissue to eliminate arrhythmia. Biomaterials have also been applied in the derivation of CMs in vitro to increase the efficiency and maturation of cardiac differentiation. Collectively, a lot has been learned from the past failures of simply injecting intact stem cells or their derivatives in vivo for treating MI, and bioengineering stem cells with biomaterials may be a valuable strategy for advancing stem cell therapy towards its widespread application for MI treatment in the clinic.

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Section: Remaining Challenges Of Using Pscs For MI Therapymentioning

confidence: 99%

Section: Remaining Challenges Of Using Pscs For MI Therapymentioning

confidence: 99%

Section: Purification Of Psc-derived Cms For MI Therapymentioning

confidence: 99%

Section: Tumorigenesis Associated With Psc-derived Cms For MI Therapymentioning

confidence: 99%

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Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Jiang

Shamul

et al. 2020

Advanced Therapeutics

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“…For example, knockdown of both HLA class I and class II in hESC could provoke T-cell ignorance in vitro and protection from xenogeneic immune rejection in vivo (60–62). Disruption of MHC class II transactivator in hESCs leads to the silencing of HLA class II expression in differentiated cells, such genetic modification could confer protection from the allogeneic helper T cells (63, 64). While the immune evasive properties of these cells lacking HLA I and II molecules have been confirmed in vitro and in mice, they remain to be evaluated in the context of a human immune system.…”

Section: Strategies To Protect Allogeneic Human Pluripotent Stem Cellmentioning

confidence: 99%

The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives

Liu

et al. 2017

Front. Immunol.

122

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Human embryonic stem cells (hESCs) can undergo unlimited self-renewal and differentiate into all cell types in human body, and therefore hold great potential for cell therapy of currently incurable diseases including neural degenerative diseases, heart failure, and macular degeneration. This potential is further underscored by the promising safety and efficacy data from the ongoing clinical trials of hESC-based therapy of macular degeneration. However, one main challenge for the clinical application of hESC-based therapy is the allogeneic immune rejection of hESC-derived cells by the recipient. The breakthrough of the technology to generate autologous-induced pluripotent stem cells (iPSCs) by nuclear reprogramming of patient’s somatic cells raised the possibility that autologous iPSC-derived cells can be transplanted into the patients without the concern of immune rejection. However, accumulating data indicate that certain iPSC-derived cells can be immunogenic. In addition, the genomic instability associated with iPSCs raises additional safety concern to use iPSC-derived cells in human cell therapy. In this review, we will discuss the mechanism underlying the immunogenicity of the pluripotent stem cells and recent progress in developing immune tolerance strategies of human pluripotent stem cell (hPSC)-derived allografts. The successful development of safe and effective immune tolerance strategy will greatly facilitate the clinical development of hPSC-based cell therapy.

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Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications

Jiang¹,

Li²,

Wang³

et al. 2019

Stem Cells

Self Cite

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Despite the long discrepancy over their definition, heterogeneity, and functions, mesenchymal stem cells (MSCs) have proved to be a key player in tissue repair and homeostasis. Generally, somatic tissue-derived MSCs (st-MSCs) are subject to quality variations related to donated samples and biosafety concern for transmission of potential pathogens from the donors. In contrast, human pluripotent stem cells (hPSCs) are unlimited in supply, clear in the biological background, and convenient for quality control, genetic modification, and scale-up production. We, and others, have shown that hPSCs can differentiate in two dimensions or three dimensions to MSCs (ps-MSCs) via embryonic (mesoderm and neural crest) or extraembryonic (trophoblast) cell types under serum-containing or xeno-free and defined conditions. Compared to st-MSCs, ps-MSCs appear less mature, proliferate faster, express lower levels of inflammatory cytokines, and respond less to traditional protocols for st-MSC differentiation to other cell types, especially adipocytes. Nevertheless, ps-MSCs are capable of immune modulation and treatment of an increasing number of animal disease models via mitochondria transfer, paracrine, exosomes, and direct differentiation, and can be potentially used as a universal and endless therapy for clinical application. This review summarizes the progress on ps-MSCs and discusses perspectives and challenges for their potential translation to the clinic. STEM CELLS 2019;37:572-581 SIGNIFICANCE STATEMENTThis article provides a thorough and timely review of the history, progress, challenges, and perspective of mesenchymal stem cells derived from human pluripotent cells as a promising, qualitycontrollable, and unlimited source for therapeutic application.The unique advantages of ps-MSCs over st-MSCs include unlimited supply, more convenience for quality control, genetic manipulation, and scalable production, lower cost, and higher purity (Table 1). Below, we will introduce the history and latest advancements we and others have achieved in ps-MSC generation and study in vitro and in animal disease models, in comparison with st-MSCs. We will also discuss the perspectives and challenges for research and clinical application of ps-MSCs.

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Concise Review: One Stone for Multiple Birds: Generating Universally Compatible Human Embryonic Stem Cells

Cited by 36 publications

References 55 publications

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

Stem Cell Therapy of Myocardial Infarction: A Promising Opportunity in Bioengineering

The Immunogenicity and Immune Tolerance of Pluripotent Stem Cell Derivatives

Concise Review: Mesenchymal Stem Cells Derived from Human Pluripotent Cells, an Unlimited and Quality-Controllable Source for Therapeutic Applications

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