Hemangio colony forming cells and non-engrafting hemangio cells

Abstract

Methods of generating and expanding human hemangio-colony forming cells and non-engrafting hemangio cells in vitro and methods of expanding and using such cells are disclosed. The methods permit the production of large numbers of hemangio-colony forming cells, non-engrafting hemangio cells as well as derivative cells, such as hematopoietic and endothelial cells. The cells obtained by the methods disclosed may be used for a variety of research, clinical, and therapeutic applications. Human non-engrafting hemangio cells are a novel progenitor cell population that is related to but distinct from the hemangioblast and human hemangio-colony forming cells. The invention also provides compositions, preparations, and solutions comprising hemangio-colony forming cells, non-engrafting hemangio cells or cells differentiated therefrom. The compositions, preparations, and solutions include cryopreserved preparations and substantially purified preparations, as well as mixed compositions formulated in combination with related hemangioblast progenitor cell types that can engraft into the bone marrow.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of priority under 35 U.S.C. §121 as a divisional of U.S. patent Ser. No. 12 / 991,096 filed Nov. 4, 2010 (now U.S. Pat. No. 9,410,123), which is the National Phase of International Application No. PCT / US2009 / 043043 filed May 6, 2009, now expired, which designated the U.S. and that International Application was published under PCT Article 21(2) in English, which also includes a claim of priority under 35 U.S.C. §119(e) to U.S. provisional patent application No. 61 / 190,282 filed Aug. 26, 2008, now expired, and U.S. provisional patent application No. 61 / 126,802 filed May 6, 2008, now expired, the entirety of which is hereby incorporated by reference.FIELD OF INVENTION[0002]The present invention generally relates to methods for generating and expanding human hemangio colony forming cells and non-engrafting hemangio cells.[0003]Particularly, the invention relates to a method of generating and expanding human h...

AI Technical Summary

Benefits of technology

This method enables the production of large quantities of human hemangioblasts and hematopoietic cells, overcoming donor matching issues and addressing blood supply shortages, while providing a reliable source for therapeutic applications, including transplantation and blood transfusions.

Problems solved by technology

Despite the widespread clinical utility of HSC transplantation, the three major sources of HSCs (human bone marrow, mobilized peripheral blood, and umbilical cord blood) are limited as two-thirds of the patients in need of somatic HSC transplantation lack well-matched donors.

Although matching the MHC molecules of a transplant to those of the recipient significantly improves the success rate of clinical transplantation, it does not prevent rejection, even when the transplant is between HLA-identical siblings.

However the number of people in need of a cell or tissue transplant, such as an HSC transplant, is far greater than the available supply of cells and tissues suitable for transplantation.

Under these circumstances, it is not surprising that obtaining a good match between the MHC proteins of a recipient and those of the transplant is frequently impossible.

Therefore, many transplant recipients must wait for an MHC-matched transplant to become available or accept a transplant that is not MHC-matched and endure higher doses of immunosuppressive drugs and still risk rejection.

Further, the deletion of either Flk1 or Flt1, which are both receptors for vascular endothelial growth factor (VEGF), results in a disruption of hematopoietic and endothelial development in the mouse embryo.

Moreover, no method or conditions exist for the expansion of the hemangioblast precursor cells in vitro.

The Red Cross and other suppliers of blood report a near constant shortage of blood.

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