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

Ami Patel, Cara Marie Clementelli, Danuta Jarocha, Gohar Mosoyan, Cindy Else, Manisha Kintali, Helen Fong, Jay Tong, Ronald Gordon, Virginia Gillespie, Alla Keyzner, Mortimer Poncz, Ronald Hoffman, Camelia Iancu-Rubin

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish
Pages (from-to)3698-3713
Number of pages16
Issue number12
StatePublished - 1 Dec 2019


Dive into the research topics of 'Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice'. Together they form a unique fingerprint.

Cite this