Current Status of Induced Pluripotent Stem Cells

Neurological disorder is a general term used for diseases affecting the function of the brain and nervous system. Those include a broad range of diseases from developmental disorders (e.g., Autism) over injury related disorders (e.g., stroke and brain tumors) to age related neurodegeneration (e.g., Alzheimer's disease), affecting up to 1 billion people worldwide. For most of those disorders, no curative treatment exists leaving symptomatic treatment as the primary mean of alleviation. Human induced pluripotent stem cells (hiPSC) in combination with animal models have been instrumental to foster our understanding of underlying disease mechanisms in the brain. Of specific interest are patient derived hiPSC which allow for targeted gene editing in the cases of known mutations. Such personalized treatment would include (1) acquisition of primary cells from the patient, (2) reprogramming of those into hiPSC via non-integrative methods, (3) corrective intervention via CRISPR-Cas9 gene editing of mutations, (4) quality control to ensure successful correction and absence of off-target effects, and (5) subsequent transplantation of hiPSC or pre-differentiated precursor cells for cell replacement therapies. This would be the ideal scenario but it is time consuming and expensive. Therefore, it would be of great benefit if transplanted hiPSC could be modulated to become invisible to the recipient's immune system, avoiding graft rejection and allowing for allogenic transplantations. This review will focus on the current status of gene editing to generate non-immunogenic hiPSC and how these cells can be used to treat neurological disorders by using cell replacement therapy. By providing an overview of current limitations and challenges in stem cell replacement therapies and the treatment of neurological disorders, this review outlines how gene editing and non-immunogenic hiPSC can contribute and pave the road for new therapeutic advances. Finally, the combination of using non-immunogenic hiPSC and in vivo animal modeling will highlight the importance of models with translational value for safety efficacy testing; before embarking on human trials.

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Induced Pluripotent Stem Cells(iPS Cells):Current Status and Future Prospect*

PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS ◽

10.3724/sp.j.1206.2008.00794 ◽

2009 ◽

Vol 2009 (8) ◽

pp. 950-960 ◽

Cited By ~ 3

Author(s):

Hong-Fen SHEN ◽

Zhi-Fang YAO ◽

Gao-Fang XIAO ◽

Jun-Shuang JIA ◽

Dong XIAO ◽

...

Keyword(s):

Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Future Prospect ◽

Ips Cells ◽

Current Status ◽

Induced Pluripotent

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Application of Cord Blood and Cord Blood-Derived Induced Pluripotent Stem Cells for Cartilage Regeneration

Cell Transplantation ◽

10.1177/0963689718794864 ◽

2018 ◽

Vol 28 (5) ◽

pp. 529-537 ◽

Cited By ~ 3

Author(s):

Yeri Alice Rim ◽

Yoojun Nam ◽

Ji Hyeon Ju

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Articular Cartilage ◽

Cord Blood ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Current Status ◽

Induced Pluripotent

Regeneration of articular cartilage is of great interest in cartilage tissue engineering since articular cartilage has a low regenerative capacity. Due to the difficulty in obtaining healthy cartilage for transplantation, there is a need to develop an alternative and effective regeneration therapy to treat degenerative or damaged joint diseases. Stem cells including various adult stem cells and pluripotent stem cells are now actively used in tissue engineering. Here, we provide an overview of the current status of cord blood cells and induced pluripotent stem cells derived from these cells in cartilage regeneration. The abilities of these cells to undergo chondrogenic differentiation are also described. Finally, the technical challenges of articular cartilage regeneration and future directions are discussed.

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Current status and future perspectives of HLA-edited induced pluripotent stem cells

Inflammation and Regeneration ◽

10.1186/s41232-020-00132-9 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Keiko Koga ◽

Bo Wang ◽

Shin Kaneko

Keyword(s):

Stem Cells ◽

Regenerative Medicine ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Ethical Issues ◽

Es Cells ◽

Embryonic Stem ◽

The Body ◽

Current Status ◽

Induced Pluripotent

Abstract In 2007, Human-induced pluripotent stem cells (iPSCs) were generated by transducing four genes (Oct3/4, Sox2, Klf4, c-Myc). Because iPSCs can differentiate into any types of cells in the body and have fewer ethical issues compared to embryonic stem (ES) cells, application of iPSCs for regenerative medicine has been actively examined. In fact, iPSCs have already been used for clinical applications, but at present, only autologous iPSC-derived grafts or HLA homozygous iPSC-derived grafts are being transplanted into patients following HLA matching. HLA is an important molecule that enables the immune system differentiates between self and non-self-components; thus, HLA mismatch is a major hurdle in the transplantation of iPSCs. To deliver inexpensive off-the-shelf iPSC-derived regenerative medicine products to more patients, it is necessary to generate universal iPSCs that can be transplanted regardless of the HLA haplotypes. The current strategy to generate universal iPSCs has two broad aims: deleting HLA expression and avoiding attacks from NK cells, which are caused by HLA deletion. Deletion of B2M and CIITA genes using the CRISPR/Cas9 system has been reported to suppress the expression of HLA class I and class II, respectively. Transduction of NK inhibitory ligands, such as HLA-E and CD47, has been used to avoid NK cell attacks. Most recently, the HLA-C retaining method has been used to generate semi-universal iPSCs. Twelve haplotypes of HLA-C retaining iPSCs can cover 95% of the global population. In future, studying which types of universal iPSCs are most effective for engraftment in various physiological conditions is necessary.

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