Platelet BioGenesis ("PBG") is a Harvard University spinout that is making human platelets from stem cells. PBG have developed and patented a microfluidic bioreactor, and shown that functional platelets can be generated from human pluripotent stem cell cultures (iPSCs). By removing the volunteer donor, PBG can make platelets that are cheaper, safer, and available on demand.

To produce platelets in the body, parent cells called megakaryocytes sit adjacent sinusoidal blood vessels in the bone marrow through which they extend and sequentially release platelets into the circulation. PBG hypothesized that by creating megakaryocytes from hiPSCs using scalable serum- and feeder-free cell culture protocols, and exposing them to the architecture and intravascular shear stresses characteristic of their native microenvironment, PBG could trigger production of functional platelets.

In collaboration with Ocata Therapeutics in 2014, PBG showed that it was feasible to generate functional megakaryocytes from research-grade hiPSC cultures. The decision to begin with a hiPSC line offered genetic control of the product, supporting the future development of HLA-matched platelets that could be customized to recipients and targeted to particular diseases. This method also permitted the cryopreservation of megakaryocyte progenitors, which could be thawed and differentiated to mature megakaryocytes within a few days, facilitating future on-demand production. Most importantly however, this approach employed a serum- and feeder cell layer-free protocol which decreased the risk of an immunogenic reaction in humans, improved scalability, increased time efficiency from megakaryocyte progenitor to platelet and decreased the overall cost of platelet unit generation.

To trigger platelet production, PBG created an integrated microfluidic platform that combined novel concepts in bone marrow physiology with biologically-inspired tissue engineering. By modeling bone marrow architecture ex-vivo, and exposing megakaryocytes to shear stresses characteristic of flowing blood, PBG found that they could reproduce physiological platelet production and increase the overall rate and extent of platelet release.

In order to make platelets in the lab PBG needed to solve the supply chain from stem cell, to megakaryocyte (parent cell), to platelet. While the discovery of thrombopoietin in 1994 drove the generation of the first human platelets by Amgen in 1995, it wasn’t until 2006 that the invention of human induced pluripotent stem cells (hiPSCs) by Dr. Yamanaka alloPBGd for the scalable generation of genetically consistent stem cells. The third major advance was made in 2014, when PBG solved how to trigger megakaryocytes to make platelets at yields necessary for clinical/commercial application.


Podcast: PBG interview via Digital Biotech (Db)

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