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Transfusion. 2019 Dec;59(12):3698-3713. doi: 10.1111/trf.15546. Epub 2019 Nov 5.

Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice.

Author information

1
Division of Hematology and Medical Oncology, Tisch Cancer Institute and the Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
2
Division of Hematology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
3
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
4
Comparative Pathology Laboratory in the Center for Comparative Medicine and Surgery, Icahn School of Medicine at Mount Sinai, New York, New York.
5
Sangamo Therapeutics, Inc., Richmond, California.
6
AllCells, LLC, Alameda, California.
7
Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
8
Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Abstract

BACKGROUND:

Platelet (PLT) transfusions are the most effective treatments for patients with thrombocytopenia. The growing demand for PLT transfusion products is compounded by a limited supply due to dependency on volunteer donors, a short shelf-life, risk of contaminating pathogens, and alloimmunization. This study provides preclinical evidence that a third-party, cryopreservable source of PLT-generating cells has the potential to complement presently available PLT transfusion products.

STUDY DESIGN AND METHODS:

CD34+ hematopoietic stem/progenitor cells derived from umbilical cord blood (UCB) units were used in a simple and efficient culture system to generate a cell product consisting of megakaryocytes (MKs) at different stages of development. The cultures thus generated were evaluated ex vivo and in vivo before and after cryopreservation.

RESULTS:

We generated a megakaryocytic cell product that can be cryopreserved without altering its phenotypical and functional capabilities. The infusion of such a product, either fresh or cryopreserved, into immune-deficient mice led to production of functional human PLTs which were observed within a week after infusion and persisted for 8 weeks, orders of magnitude longer than that observed after the infusion of traditional PLT transfusion products. The sustained human PLT engraftment was accompanied by a robust presence of human cells in the bone marrow (BM), spleen, and lungs of recipient mice.

CONCLUSION:

This is a proof-of-principle study demonstrating the creation of a cryopreservable megakaryocytic cell product which releases functional PLTs in vivo. Clinical development of such a product is currently being pursued for the treatment of thrombocytopenia in patients with hematological malignancies.

PMID:
31802511
DOI:
10.1111/trf.15546

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