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With ‘simple method,’ stem cells used to make platelets for transfusion

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January 9, 2019

Yumika Matsubara, PhD
Yumika Matsubara

Adipose-derived mesenchymal stem cell lines could be used to manufacture platelets that may serve as an alternative to donor-dependent platelet transfusions, according to research published in Blood.

“By removing the donor from the equation, adipose-derived stem cells could be used to provide a ready supply of safe, tolerable platelets to meet an ever-changing demand,” researcher Yumika Matsubara, PhD, of Keio University School of Medicine in Tokyo, said in a press release.

The clinical need for platelets is increasing, with more than 4.5 million platelet units of plasma transferred worldwide each year, according to the press release.

“Platelet transfusions, however, are donor-dependent and associated with severe problems, such as a limited supply due to their short shelf life (eg, 5 days in the U.S.), and the risk of bacterial infection and serious immune reactions,” researchers wrote. “The development of an efficient production system for platelets from a donor-independent source to obviate these concerns is therefore crucial.”

Platelets are released from megakaryocytes after several processes. First, stem cells differentiate into immature megakaryocytes, and then into mature megakaryocytes, which release platelets. In a previous study of induced pluripotent stem cells, researchers noticed adipose-derived cells — being used as the negative control — had produced megakaryocyte- and platelet-sized cells that expressed genes associated with platelet production.

Based on this observation, Matsubara and colleagues obtained subcutaneous adipose tissue from patients undergoing reconstructive surgery after tumorectomy at Keio University Hospital. Researchers then created a manufacturing system for platelets using human adipose-derived mesenchymal stromal/stem lines (ASCL).

Researchers obtained ASCL-derived megakaryocytes when they peaked at day 8 of culture, and ASCL-derived platelets when they peaked at day 12 of culture.

Researchers then tested these manufactured platelets to see if they would function similar to natural platelets based on protein expression and blood clotting simulations.

Results showed that CD42b-positive cells expressed mesenchymal stem cell marker CD90 in association with cell adhesion.

When compared with peripheral platelets, ASCL-derived platelets demonstrated higher levels of PAC1 binding and P-selectin surface exposure — both markers for platelet activation — as well as ristocetin-induced and ADP-induced platelet aggregation.

Peripheral platelets and ASCL-derived platelets demonstrated similar levels of fibrinogen binding and collagen-induced platelet aggregation, whereas ASCL-derived platelets showed lower epinephrine-induced platelet aggregation.

ASCL-derived platelets showed a pattern of in vivo kinetics comparable to that of platelet concentrates after being infused into irradiated immunodeficient mice.

Overall, gene transfer is not required to establish ASCL or its differentiation into ASCL platelets, which is achieved through the use of endogenous thrombopoietin. The current procedure is simple and does not call for feeder cells, researchers wrote.

“Though more expensive to harvest compared [with] donor-derived platelets, this research demonstrates that platelets can be produced from adipose-derived cells by a rather simple method,” Matsubara said in the press release. “Now that we have established an efficient manufacturing process to yield a large number of adipose-derived platelets, we next plan to perform preclinical studies using animal models to demonstrate efficacy and safety, followed by clinical trials in human patients.” – by Jennifer Byrne

Disclosures : Matsubara reports research funding from AdipoSeeds, Fujimori Kogyo, Nissui Pharmaceutical and Tosoh, and interests in AdipoSeeds. Please see the study for all other authors’ relevant financial disclosures.