Plasma-depleted, non-red blood cell-depleted cord blood compositions and methods of use

Abstract

The umbilical cord blood (UCB) compositions of the present invention possess the unique features of having plasma that is substantially depleted from the UCB unit and red blood cells (RBC) that are not depleted from the UCB unit. Such UCB units can be prepared by a process that combines plasma depletion with cryopreservation, selection, thawing, and / or transplantation of hematopoietic stem cells to provide superior clinical outcome by maximizing post-processing cell recovery and post-thaw infusion cell dose. Methods for treating a wide variety of malignant diseases and benign diseases associated with the hematopoietic system by administering the UCB compositions of the present invention are also provided.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is related to U.S. Provisional Application Nos. 60 / 687,127, filed Jun. 2, 2005, and 60 / 733,956, filed Nov. 3, 2005, the disclosures of which are hereby incorporated by reference in their entirety for all purposes.BACKGROUND OF THE INVENTION [0002] There is considerable interest in the identification, isolation and generation of human stem cells. Human stem cells are totipotential or pluripotential precursor cells capable of self renewal and generating a variety of mature human cell lineages. This ability serves as the basis for the cellular differentiation and specialization necessary for organ and tissue development. Recent success at transplanting stem cells have provided new clinical tools to reconstitute and / or supplement bone marrow after myeloablation due to disease, exposure to toxic chemicals, and / or radiation. Further evidence exists that demonstrates that stem cells can be employed to repopulate many, if not ...

AI Technical Summary

Benefits of technology

[0009] The umbilical cord blood (UCB) compositions of the present invention possess the advantageous features of having plasma that is substantially depleted but red blood cells (RBC) that are not depleted from the UCB unit, i.e., a plasma-depleted, non-red blood cell-depleted composition. Such UCB units can be prepared by a process that combines plasma depletion with cryopreservation, selection, thawing, and / or transplantation of hematopoietic stem cells to provide superior clinical outcomes relative to whole blood or RBC-depleted UCB units by maximizing post-processing cell recovery and post-thaw infusion cell dose. Methods for treating a wide variety of malignant diseases and benign diseases associated with the hematopoietic system by administering the UCB compositions of the present invention are also provided.

[0018] In other embodiments of the present invention, the plasma-depleted UCB composition that is administered to the mammalian subject for the treatment or curative transplantation of hematopoietic diseases provides one or more of the following superior clinical outcomes: (1) an increase in the cumulative incidence of neutrophil engraftment relative to whole cord blood or red blood cell-depleted cord blood; (2) an increase in the cumulative incidence of platelet engraftment relative to whole cord blood or red blood cell-depleted cord blood; (3) an increase in the speed to neutrophil engraftment relative to whole cord blood or red blood cell-depleted cord blood; (4) an increase in the speed to platelet engraftment relative to whole cord blood or red blood cell-depleted cord blood; (5) an increase in the disease free survival rate relative to whole cord blood, red blood cell-depleted cord blood, bone marrow, or peripheral blood stem cells; (6) a decrease in the transplant related mortality rate relative to whole cord blood, red blood cell-depleted cord blood, bone marrow, or peripheral blood stem cells; (7) an increase in the overall survival rate relative to whole cord blood, red blood cell-depleted cord blood, bone marrow, or peripheral blood stem cells; and (8) a decrease in the incidence of acute and chronic graft versus host disease relative to bone marrow or peripheral blood stem cells. As used herein, an increase or decrease in one of the above-described clinical outcomes refers to a difference of at least about 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50%, relative to whole cord blood, red blood cell-depleted cord blood, bone marrow, and / or peripheral blood stem cells. Preferably, the plasma-depleted UCB composition that is administered to the mammalian subject provides at least one, two, three, four, five, six, or more of the above-described clinical outcomes.

Problems solved by technology

Because of the tens of millions of possible combinations of HLA types in the population, a basic problem remains, in that it is very difficult to obtain sufficient quantities, populations, and varieties of HLA types of human stem cells which are capable of differentiating into all cell types that can be HLA matched to individual patients.

Obtaining sufficient numbers of human stem cells has been problematic for several reasons.

First, isolation of normally occurring populations of stem cells in adult tissues has been technically difficult and costly due, in part, to very limited quantities found in blood or tissue.

Second, procurement of these cells from embryos or fetal tissue, including aborted fetuses, has raised ethical concerns.

There are, however, few viable alternative sources of stem cells, particularly human stem cells, and thus the supply is limited.

Furthermore, harvesting of stem cells from alternative sources in adequate amounts for therapeutic and research purposes is generally laborious, involving, e.g., harvesting of cells or tissues from a donor subject or patient, culturing and / or propagation of cells in vitro, dissection, etc.

The drawback of such methods, however, is that they first require the invasive and painful harvesting of marrow or periosteal cells from a human donor in order to subsequently isolate HMSCs.

The drawback of such methods, however, is that they are labor-intensive and the yield of stem cells is very low.

A major limitation of stem cell procurement from cord blood, however, has been the frequently inadequate volume of cord blood obtained, resulting in insufficient cell numbers to effectively reconstitute bone marrow after transplantation.

However, stem cells from umbilical cord blood are in critically short supply due to restrictions on their collection, the inadequate numbers of cells typically collected from cord blood, especially if used to treat an adult patient, and the extraordinary cost of establishing a large inventory.

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