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Developments in Artificial Platelet and Erythroid Transfusion Products

Part of the Advances in Experimental Medicine and Biology book series (CBTMED,volume 1247)

Abstract

Platelet and blood transfusions have vital importance to the lives of many patients. Platelet transfusions are a life-saving intervention by reducing risk of bleeding in thrombocytopenic patients. Due to the short shelf life of platelets and their limited availability, researchers have developed various platelet transfusion production technologies. Understanding the cellular and biophysical mechanisms of platelet release is particularly important for development of platelet transfusion products (PTPs) and to translate them to clinical applications in patients requiring platelet infusion. Similarly, due to donor dependence and increased clinical need of blood transfusions, studies on the erythroid transfusion products (ETPs) have recently gained momentum. This led to development of ETP technologies involving differentiation of stem cells to fully functional erythrocytes in vitro. During megakaryopoiesis or erythropoiesis, various stimulatory factors, growth factors, transcription factors, and biophysical conditions have been shown to play a crucial role in the formation final blood products. Thus, understanding of the in vivo mechanisms of platelet release and erythrocyte maturation is particularly important for mimicking these conditions in vitro. This review focuses on latest and up-to-date information about the innovations in PTP and ETP technologies. We also discuss some of the recent fundamental findings that have changed our understanding of in vivo platelet release and blood formation.

Graphical Abstract

Human bone marrow acts as a source of cells required for erythropoiesis and megakaryopoeiesis. Understanding of molecular mechanism and physiology of these vital and curitial events allowed us to mimic these conditions ex vivo and to develop artificial platelet and erythroid transfusion production technologies.

Keywords

  • Erythroid transfusion products
  • Erythropoiesis
  • ETPs
  • Hematopoietic stem cells
  • Megakaryocytopoiesis
  • Megakaryopoeiesis
  • Platelet transfusion products

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Abbreviations

ABI:

Aurora B Inhibitor

ADSC:

Adipose Derived Stem Cells

BFU-MK:

Burst Forming Unit Megakaryocyte

BM:

Bone Marrow

CFU-GEMM:

Colony Forming Unit – granulocyte, erythrocyte, monocyte, megakaryocyte

CFU-Mk:

Colony Forming Unit Megakaryocyte

CMP:

Common Myeloid Progenitor

CMPs:

Common Myeloid Progenitors

DMS:

Demarcation Membrane System

ECM:

Extracellular Matrix

ESC:

Embryonic Stem Cell

ES-sacs:

Embryonic Stem Cell–Derived Sacs

ETPs:

Erythroid Transfusion Products

FLI1:

Friend Leukemia Integration 1

GATA1:

GATA binding protein 1

GPV:

Glycoprotein V

HDFs:

Human Dermal Fibroblasts

hESCs:

Human Embryonic Stem Cells

hiPSCs:

Human Induced Pluripotent Stem Cells

HPC:

Hematopoietic Progenitor Cells

HSC:

Hematopoietic Stem Cell

hTERT:

Human telomerase reverse transcriptase

IL-1α:

Interleukin 1 alpha

MAPK:

Mitogen Activated Protein Kinase

Meis1:

Myeloid ectopic viral integration site 1

MEP:

Megakaryocyte Erythroid Progenitor

Mk:

Megakaryocyte

MKP:

Megakaryocyte Progenitor

Mks:

Megakaryocytes

NF-E2:

Nuclear Factor Erythroid 2

PB:

Peripheral Blood

PDGF:

Platelet Derived Growth Factor

PI:

Phosphatidylinositol

PTPs:

Platelet Transfusion Products

RBCs:

Red Blood Cells

RRI:

Rho Rock inhibitor

RUNX1:

Runt related transcription factor 1

SCF:

Stem Cell Factor

SDF-1:

Stromal-Derived Factor-1

SI:

Src Inhibitor

STAT1:

Signal Transducer and Activator of Transcription 1

TAL-1:

T-cell Acute Lymphocytic Leukemia Protein 1

TGF-β:

Transforming Growth Factor-Beta

TPO:

Thrombopoietin

UCB:

Umbilical Cord Blood

VEGF:

Vascular Endothelial Growth Factor

vWF:

von Willebrand Factor

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Acknowledgments

FK has been supported by funds provided by the European Commission Co-Funded Brain Circulation Scheme by The Marie Curie Action COFUND of the 7th. Framework Programme (FP7) (115C039), The Scientific and Technological Research Council of Turkey (TÜBİTAK) [grant numbers 115S185, 215Z069, 215Z071,and 216S317], The Science Academy Young Scientist Award Program (BAGEP-2015, Turkey), The International Centre for Genetic Engineering and Biotechnology – ICGEB 2015 Early Career Return Grant [grant number CRP/TUR15-02_EC], Medicine for Malaria Venture MMV Pathogenbox Award (Bill and Melinda Gates Foundation), Gilead Sciences International Hematology & Oncology program, Gilead ile Hayat Bulan Fikirler, and ERA-Net CVD program (118S929). We apologize whose work could not be discussed in this review due to size limitations. All authors declare that they have no conflicts of interest concerning this work.

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Meric, N., Guney Esken, G., Uslu, M., Kocabas, F. (2019). Developments in Artificial Platelet and Erythroid Transfusion Products. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 8. Advances in Experimental Medicine and Biology(), vol 1247. Springer, Cham. https://doi.org/10.1007/5584_2019_455

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