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Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells

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Abstract

Platelets (PLTs) are small anucleate blood cells that release from polyploidy megakaryocytes(MKs). PLT transfusion is standard therapy to prevent hemorrhage. PLT transfusion is donor‐dependent way which have limitations including the inadequate donor blood supply, poor quality, and issues related to infection and immunity. Overcoming these obstacles is possible with in vitro production of human PLTs. Currently several cells have been considered as source to in vitro production of PLTs such as hematopoietic stem cells (HSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, HSCs are a limited source for PLT production and large-scale expansion of HSC-derived PLT remains difficult. Alternative sources can be ESCs which have unlimited expansion capacity. But ESCs have ethical issues related to destroying human embryos. iPSCs are considered as an ideal unlimited source for PLT production. They are able to differentiate into any cells and have the capacity of self-renewal. Moreover, iPSCs can be acquired from any donor and easily manipulated. Due to new advances in development of MK cell lines, bioreactors, feeder cell-free production and the ability of large scale generation, iPSC-based PLTs are moving toward clinical applicability and considering the minimal risk of alloimmunization and tumorigenesis of these products, there is great hopefulness they will become the standard source for blood transfusions in the future. This review will focus on how to progress of in vitro generation of PLT from stem cell especially iPSCs and some of the successful strategies that can be easily used in clinic will be described.

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Abbreviations

iPSCs:

Induced Pluripotent Stem Cells

hiPSC:

Human Induced Pluripotent Stem Cells

PLTs:

Platelets

MKs:

Megakaryocytes

PRP:

Platelet-Rich Plasma

BM:

Bone marrow

PB:

Peripheral Blood

HLA:

Human Leukocyte Antigen

HPA:

Human Platelet Antigen

hPSCs:

Human pluripotent stem cells

PTR:

Platelets Transfusion Refractoriness

TRALI:

Transfusion-Related Acute Lung Injury

UCB:

Umbilical Cord Blood

HSCs:

Hematopoietic stem cells

TPO:

Thrombopoietin

SCF:

Stem Cell Factor

ESCs:

Embryonic Stem Cells

hESCs:

Human Embryonic Stem Cells

VEGF:

Vascular Endothelial Growth Factor

ES-sacs:

Embryonic Stem Cell–Derived Sacs

HPCs:

Hematopoietic Progenitor Cells

TF:

Transcription Factors

YFs:

Yamanaka factors

EB:

Embryoid Body

MEF:

Murine Embryonic Fibroblast

HDF:

Human Dermal Fibroblasts

ciPSCs:

Canine Induced Pluripotent Stem Cells

imMKCLs:

Immortalize MK Progenitor Cell Line

MK-FOP:

MK Forward Programming

MMPs:

Matrix Metalloproteinase

vWF:

Von Willebrand Factor

GPIbα:

Platelet Glycoprotein Ibα

GVHD:

Graft-versus-host disease

B2M:

β2-Microglobulin

KO:

Knockout

CDC:

Cellular-dependent Cytotoxicity

ADCC:

Antibody-dependent Cell-mediated Cytotoxicity

FNAIT:

Fetal/neonatal Alloimmune Thrombocytopenia

PTP:

Post-Transfusion Purpura

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Acknowledgements

We acknowledge the staffs of Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran university of medical sciences, Tehran, Iran.

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Authors and Affiliations

  1. Stem Cell and Regenerative Medicine Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran

    Elaheh Izady, Zohreh Saltanatpour & Amir Ali Hamidieh

  2. Pediatric Cell and Gene Therapy Research Center, Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran

    Zohreh Saltanatpour & Amir Ali Hamidieh

  3. Institute of Regenerative Medicine, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang Jiangsu, 212001, China

    Li-Ping Liu

  4. Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Akram Alizadeh

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  1. Elaheh Izady
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EI and ZS were contributed in paper writing and generated figures. AAH were contributed in data discussion and revised the manuscript LPL and AA were contributed in revised the manuscript.

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Izady, E., Saltanatpour, Z., Liu, LP. et al. Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells. Stem Cell Rev and Rep 18, 2376–2387 (2022). https://doi.org/10.1007/s12015-022-10366-4

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