Method for repopulating human bone marrow comprising...

Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Animal or plant cell

Reexamination Certificate

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Details

C435S389000, C435S384000, C435S404000, C435S405000, C435S407000

Reexamination Certificate

active

06224860

ABSTRACT:

BACKGROUND OF THE INVENTION
The present invention relates to a serum-free medium which can support the growth and proliferation of normal human hematopoietic CD34
+
cells purified from sources such as normal human bone marrow, the peripheral blood of patients treated with cytokines (termed mobilized CD34
+
cells) or umbilical cord blood.
The growth of these cells is becoming more important in view of recent developments in clinical regimens for combatting diseases such as cancer, myeloproliferative diseases and autoimmune diseases. However, many media are not suitable for culturing normal bone marrow cells, especially CD34
+
cells because of their high proliferative capability. Therefore, a need exists for developing a serum-free medium which can support the proliferation and differentiation of CD34
+
cells.
SUMMARY OF THE INVENTION
Since not all cells will proliferate in a single (universal) serum-free medium, care must be taken in the development of each medium. Such a medium is invaluable in the expansion of specific hematopoietic lineages for bone marrow transplantation. Such a medium will allow the potential to store small amounts of bone marrow or subsets of the bone marrow cell population (such as by freezing) and at a later time expand the cells by thawing the cells and growing them in vitro for transplantation purposes. The inventor has developed such a medium that can support CD34
+
cellular proliferation and in the presence of the appropriate cytokine(s), expand specific cell types/lineages. An advantage to this medium is that it contains components derived from U.S. Pharmaceutical grade components that will permit it to be used in clinical regimens.
It is one object of the invention to provide a serum-free medium comprising a basal medium, an effective amount of essential fatty acid, an effective amount of cholesterol, transferrin in an amount of 120 to 500 &mgr;g/ml or an effective amount of an iron salt and an effective amount of insulin growth factor, wherein said medium supports the proliferation and differentiation of normal CD34
+
cells or comprising a basal medium, an effective amount of fatty acid, an effective amount of cholesterol, an effective amount of transferrin or an effective amount of an iron salt and insulin in an amount of 0.25 to 2.5 U/ml or an effective amount of insulin like growth factor, wherein said medium supports the proliferation and differentiation of normal CD34
+
cells.
It is another object of the invention to provide a serum-free medium comprising a serum-free culture medium which supports the proliferation and differentiation of CD34
+
cells which comprises an effective amount of human serum albumin, transferrin in an amount of 130 to 500 &mgr;g/ml and insulin in an amount of 0.25 to 2.5 U/ml, wherein said human serum albumin, transferrin, and insulin are each present in an amount effective for supporting the proliferation and differentiation of CD34
+
cells.
It is another object of the invention to provide a method for growing normal CD34
+
cells which comprises cultivating said cells in one of the above defined media or in a serum-free medium comprising: human serum albumin; transferrin; and insulin, wherein each of said human serum albumin, transferrin and insulin is dissolved in a serum-free basal medium.
Various growth factors and/or cytokines for driving proliferation and differentiation of the cells can optionally be added to the medium used to culture the cells. By means of adding various cytokines, the composition of the cell population can be altered with respect to the types of cells present in the population.


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