Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing
Reexamination Certificate
1999-03-12
2002-03-12
Nguyen, Dave T. (Department: 1632)
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
C424S093200, C435S325000, C435S372000
Reexamination Certificate
active
06355239
ABSTRACT:
The present invention is directed to various methods and products for using mesenchymal stem cells (MSCs).
In accordance with an aspect of the present invention, an animal is treated with mesenchymal stem cells wherein the mesenchymal stem cells are obtained from an animal other than the animal being treated, i.e. the mesenchymal stem cells are not autologous.
More particularly, in accordance with an aspect of the invention, a patient is treated with allogeneic human mesenchymal stem cells. As the term is used herein, an allogeneic human mesenchymal stem cell is a mesenchymal stem cell obtained from a human other than the intended recipient of the mesenchymal stem cells.
Although the mesenchymal stem cells express surface MHC molecules, applicants have found that the mesenchymal stem cells are immunologically neutral and therefore can be used as described herein without inducing an adverse immune response in the recipient of the cells.
In addition, applicants have found that the donor of the mesenchymal stem cells need not be “matched” to the recipient.
In accordance with the present invention, it has been discovered that mesenchymal stem cells are “invisible” to the immune system. Normally, co-culturing cells from different individuals (allogeneic cells) results in T cell proliferation, manifested as a mixed lymphocyte reaction (MLR). However, when human mesenchymal stem cells are contacted with allogeneic T lymphocytes, in vitro, they do not generate an immune response by the T cells, i.e., the T cells do not proliferate, indicating that T cells are not responsive to mismatched mesenchymal stem cells. This discovery was unexpected because human mesenchymal stem cells express all of the surface molecules that render them immunogenic, i.e., they express allogeneic class I and class II MHC molecules.
It has also been discovered that mesenchymal stem cells actively reduce the allogeneic T cell response in mixed lymphocyte reactions in a dose dependent manner. It has further been discovered that mesenchymal stem cells from different donors do not exhibit specificity of reduced response with regard to MHC type. Thus, mesenchymal stem cells need not be MHC matched to a target cell population in the mixed lymphocyte reaction in order to reduce the proliferative response of alloreactive T cells to mesenchymal stem cells.
REFERENCES:
patent: 5226914 (1993-07-01), Caplan et al.
patent: 5591625 (1997-01-01), Gerson et al.
Z Nevo et al., Cell Transplantation, “The Manipulated Mesenchymal Stem Cells in Regenerated Skeletal Tissues,” 1998, vol. 7, No. 1, pp. 63-70.*
IM Roitt et al., Immunology, “Transplantation and Rejection,” 1993, 3rd.Ed., Chap.23, pp.23.1.*
MS Leffell et al., Handbook of Human Immunology, “DNA-based Typing of HLA for Transplantation,” CRC Press,1997,Chap.13, p. 545.*
Tse, et al., “Bone Marrow-Derived Mesenchymal Stem Cells Suppress T-Cell Activation without Inducing Allogeneic Anergy,”Journal of the American Society of Hematology,vol. 96, No. 11 (Nov. 16, 2000).
Bruder SP et al. J. Cell. Biochem. 56:283-294. 1994.*
Robinson D et al. Agents Actions Suppl 39:231-235. 1993 (abstract).*
Stiller CR et al. N Engl. J. Med. 294:978-982. 1976.*
Kissinger A J Clin. Apheresis 5:97-99. 1990 (Abstract).*
Theobald, Valerie A., et al., ““Neutral Allografts”—Lack of Allogeneic Stimulation by Cultured Human Cells Expressing MHC Class I and Class II Antigens,”Tranplantation, vol. 55, No. 1, pp. 128-133 (1993).
Goodman, et al., “Fludarabine Phosphate: A DNA Synthesis Inhibitior with Potent Immunosuppressive Activity and Minimal Clinical Toxicity,”The American Surgeon, 62(6);435-442 (1996).
Bruder Scott P.
Marshak Daniel R.
McIntosh Kevin R.
Mosca Joseph D.
Grant Alan J.
Nguyen Dave T.
Olstein Elliot M.
Osiris Therapeutics, Inc.
Shukla Ram R.
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