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Fusion proteins enable expansion of HSPCs

Bone marrow harvest

Credit: Chad McNeeley

A new technique has allowed researchers to expand hematopoietic stem and progenitor cells (HSPCs) from multiple sources.

The team developed fusion proteins and introduced them to HSPCs ex vivo.

This approach expanded cell populations whether HSPCs were derived from cord blood, bone marrow, or peripheral blood.

The potential clinical applications for this work range from immunodeficiency disorders to hematologic and other malignancies, according to the researchers.

Yosef Refaeli, PhD, of Taiga Biotechnologies, Inc. in Aurora, Colorado, and his colleagues described this work in PLOS ONE.

The team first cultured human or murine HSPCs with a pair of fusion proteins—the protein transduction domain of the HIV-1 transactivation protein (Tat) and either the Open Reading Frame for human MYC or a truncated form of human Bcl-2 that was deleted for the unstructured loop domain.

With this technique, the researchers were able to elicit an 87-fold expansion of HSPCs from mouse bone marrow, a 16.6-fold expansion of HSPCs from human cord blood, a 13.6-fold expansion of HSPCs from human peripheral blood cells mobilized by G-CSF, and a 10-fold expansion of HSPCs from human bone marrow.

The team then tested the biological function of the expanded cells, and they found the cells gave rise to BFU-E, CFU-M, CFU-G, and CFU-GM colonies in vitro.

When transplanted into irradiated mice, the expanded cells gave rise to mature hematopoietic populations and a self-renewing cell population that was able to support hematopoiesis upon serial transplantation.

The researchers said these results suggest their technique may be an attractive approach to expand human HSPCs ex vivo for clinical use.

The team’s goal now is to move the technology from the lab into clinical trials. Taiga Biotechnologies is in the process of setting up clinical trials testing this approach.

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Bone marrow harvest

Credit: Chad McNeeley

A new technique has allowed researchers to expand hematopoietic stem and progenitor cells (HSPCs) from multiple sources.

The team developed fusion proteins and introduced them to HSPCs ex vivo.

This approach expanded cell populations whether HSPCs were derived from cord blood, bone marrow, or peripheral blood.

The potential clinical applications for this work range from immunodeficiency disorders to hematologic and other malignancies, according to the researchers.

Yosef Refaeli, PhD, of Taiga Biotechnologies, Inc. in Aurora, Colorado, and his colleagues described this work in PLOS ONE.

The team first cultured human or murine HSPCs with a pair of fusion proteins—the protein transduction domain of the HIV-1 transactivation protein (Tat) and either the Open Reading Frame for human MYC or a truncated form of human Bcl-2 that was deleted for the unstructured loop domain.

With this technique, the researchers were able to elicit an 87-fold expansion of HSPCs from mouse bone marrow, a 16.6-fold expansion of HSPCs from human cord blood, a 13.6-fold expansion of HSPCs from human peripheral blood cells mobilized by G-CSF, and a 10-fold expansion of HSPCs from human bone marrow.

The team then tested the biological function of the expanded cells, and they found the cells gave rise to BFU-E, CFU-M, CFU-G, and CFU-GM colonies in vitro.

When transplanted into irradiated mice, the expanded cells gave rise to mature hematopoietic populations and a self-renewing cell population that was able to support hematopoiesis upon serial transplantation.

The researchers said these results suggest their technique may be an attractive approach to expand human HSPCs ex vivo for clinical use.

The team’s goal now is to move the technology from the lab into clinical trials. Taiga Biotechnologies is in the process of setting up clinical trials testing this approach.

Bone marrow harvest

Credit: Chad McNeeley

A new technique has allowed researchers to expand hematopoietic stem and progenitor cells (HSPCs) from multiple sources.

The team developed fusion proteins and introduced them to HSPCs ex vivo.

This approach expanded cell populations whether HSPCs were derived from cord blood, bone marrow, or peripheral blood.

The potential clinical applications for this work range from immunodeficiency disorders to hematologic and other malignancies, according to the researchers.

Yosef Refaeli, PhD, of Taiga Biotechnologies, Inc. in Aurora, Colorado, and his colleagues described this work in PLOS ONE.

The team first cultured human or murine HSPCs with a pair of fusion proteins—the protein transduction domain of the HIV-1 transactivation protein (Tat) and either the Open Reading Frame for human MYC or a truncated form of human Bcl-2 that was deleted for the unstructured loop domain.

With this technique, the researchers were able to elicit an 87-fold expansion of HSPCs from mouse bone marrow, a 16.6-fold expansion of HSPCs from human cord blood, a 13.6-fold expansion of HSPCs from human peripheral blood cells mobilized by G-CSF, and a 10-fold expansion of HSPCs from human bone marrow.

The team then tested the biological function of the expanded cells, and they found the cells gave rise to BFU-E, CFU-M, CFU-G, and CFU-GM colonies in vitro.

When transplanted into irradiated mice, the expanded cells gave rise to mature hematopoietic populations and a self-renewing cell population that was able to support hematopoiesis upon serial transplantation.

The researchers said these results suggest their technique may be an attractive approach to expand human HSPCs ex vivo for clinical use.

The team’s goal now is to move the technology from the lab into clinical trials. Taiga Biotechnologies is in the process of setting up clinical trials testing this approach.

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