Recent developments in ex vivo platelet production

Abstract

The platelet is a component of blood that functions to initiate blood clotting. Abnormal platelet count and function can lead to a life-threatening condition caused by excessive bleeding. At present, platelet supply for transfusion can be obtained only from platelet donation. However, platelets cannot be stored for longer than 7 days, meaning that routine isolation is required to maintain platelet supply for transfusion. To mitigate for potential platelet shortages, several strategies have been proposed to generate platelets ex vivo. By employing both of natural and artificial approaches, several researchers have successfully generated biomaterials with characteristics similar to human-derived platelets. Their reports indicated that the biomaterials could mimic the aggregation of human-isolated platelets, further suggesting the possibility to substitute or complement human-isolated platelets. The current review summarizes the progress in ex vivo platelet production and gives a prospect for the possible approaches to achieving a feasible platelet factory, based on the Good Manufacturing Practice standards.

Large‐scale culture of a megakaryocytic progenitor cell line with a single‐use bioreactor system

“…The recent growing interest in regenerative medicine consequently has brought a massive demand for human stem cells and their derivatives, including platelets, a blood clotting agent . A dynamic visualization suggested that platelets are released from the fragmentation of mature megakaryocytes, a derivative of hematopoietic stem cells (HSCs).…”

Towards the Manufacture of Megakaryocytes and Platelets for Clinical Application

“…According to the GMP for pharmaceutical products by the Food and Drug Administration (FDA), the in vitro manufacture of PLTs requires the consideration of following aspects [42]: (1) Safety of the progenitor cell source. The medical history of the stem cell donor should be known [18] or the cell reprogramming strategy of the source for induced pluripotent stem cells (iPSCs) need to comply with GMP.…”

“…Therefore, serum/feeder-free culture and the use of animal-free antibiotics and cytokines are recommended. (3) Any risk of contamination should be eliminated, e.g., by the use of automated culturing systems [42]. Figure 1 summarizes some of the key factors and corresponding aspects to allow the establishment of an effective protocol for the future in vitro manufacture of MKs or PLTs.…”

Large-Scale Cultures and Bioreactors for the Production of Megakaryocytes and Platelets

“…These meet the challenge to provide MKs and PLTs in adequate practicability, safety and clinical grade to satisfy the quantitative and qualitative demands for a Good Manufacturing Practice (GMP)-compliant translational perspective [6].…”

“…However, often iPSCs are generated by lentiviral mediated reprogramming. Here, optimally non-integrative vectors should be applied to reduce a potential tumorigenic risk of the derived stem cell-derived products [6].…”