Pre‐clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice. Issue 12 (5th November 2019)

• Record Type: Journal Article
• Authors: Patel, Ami; Clementelli, Cara Marie; Jarocha, Danuta; Mosoyan, Gohar; Else, Cindy; Kintali, Manisha; Fong, Helen; Tong, Jay; Gordon, Ronald; Gillespie, Virginia; Keyzner, Alla; Poncz, Mortimer; Hoffman, Ronald; Iancu‐Rubin, Camelia
• Is Part Of: Transfusion. Volume 59:Issue 12(2019)
• Page Start: 3698
• Page End: 3713
• Publication Date: 2019-11-05
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.15546
• Languages: English
• ISSNs: 0041-1132

Abstract

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.