We Mimic Human Bone Marrow to Trigger Platelet Production

  • We scale platelet production to meet human clinical need

  • We improve platelet purity to generate bacterial/viral-free

  • We produce immune-compatible human platelets that are safer for human infusion

  • We distribute bioreactor platelets to hospitals and blood banks to give to patients

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. We 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, we could trigger production of functional platelets.

In collaboration with Ocata Therapeutics in 2014, we 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, we 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, we found that we could reproduce physiological platelet production and increase the overall rate and extent of platelet release.

Why Now?

In order to make platelets in the lab we 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 allowed for the scalable generation of genetically consistent stem cells. The third major advance was made in 2014, when we solved how to trigger megakaryocytes to make platelets at yields necessary for clinical/commercial application.

Human iPSC-derived platelets are poised to become among the first stem cell-derived tissues advanced for clinical use and represent a major first step toward a sustainable, donor-free blood system. Platelet BioGenesis is the realization of this vision.