Creative Medical Technologies, Inc.

Disclosed are means, methods and compositions of matter useful for prevention and/or reversion of type 1 diabetes by upregulation of myeloid suppressor cell activity in a mammal suffering from and/or at risk of developing type 1 diabetes. In one embodiment the invention teaches administration of immune cells that have been conditioned by exposure to regenerative cells, and/or cultured in the presence of factors produced from regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells. In one embodiment, immune cells that have been exposed to said regenerative cells are administered together with agents known to enhance myeloid suppressor cell activity. In another embodiment immune cells are administered together with exogenous myeloid suppressor cells. 2

Methods of reducing death, destruction or rejection of beta islets along with peripheral receptors in patients before they have diabetes, wherein said method comprising the steps of: a) obtaining a patient in need of immune cell therapy; b) administering to said patient one or more immunomodulatory cells; c) assessing the prevention and transition to diabetes.

Methods of improving muscle receptor sensitivity to insulin muscle receptors, reducing death, destruction or rejection of beta islets in patients having insulin dependent diabetes, wherein said method comprising the steps of: a) obtaining a patient in need of immune cell therapy; b) administering to said patient immunomodulatory cells; c) assessing the prevention and transition to diabetes requiring insulin.

Disclosed are means, methods and compositions of matter useful for prevention and/or reversion of type 1 diabetes by upregulation of myeloid suppressor cell activity in a mammal suffering from and/or at risk of developing type 1 diabetes. In one embodiment the invention teaches administration of immune cells that have been conditioned by exposure to regenerative cells, and/or cultured in the presence of factors produced from regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells. In one embodiment, immune cells that have been exposed to said regenerative cells are administered together with agents known to enhance myeloid suppressor cell activity. In another embodiment immune cells are administered together with exogenous myeloid suppressor cells.

Compositions of matter and treatment protocols for reducing or completely avoiding the need for immune suppression in the context of allograft or xenograft transplantation. Use of mesenchymal stem cells, manipulated mesenchymal stem cells, iPSC derived mesenchymal stem cells, and products of said mesenchymal stem cells for promoting the process of immunological tolerance. In one embodiment the invention provides the use of third party “universal donor” iPSC gene edited mesenchymal stem cells to promote tolerance in context of a solid organ transplant such as renal, cardiac, hepatic or small intestine. In other embodiments endogenous mesenchymal stem cells in composite tissue allografts are activated and/expanded in order to promote tolerogenesis and reduced need for immune suppression.

Disclosed are methods, protocols and compositions of matter using for treatment of ovarian failure through administration of cells expressing FoxP3 as a monotherapy or as a facilitator to enhance therapeutic efficacy of cells and/or cytokines. In one embodiment FoxP3 expressing cells are concentrated from allogeneic umbilical cord blood, activated ex vivo with anti-CD3 and anti-CD28 antibodies and administered into the ovary alone or with regenerative cells such as stem cells. In one embodiment stem cells administered are of the CD105 expressing lineage.

Described are protocols, compositions of matter and therapeutic means useful for treatment of ovarian failure caused by oncology treatments. The utilization of natural killer cells allows for dual activity of tissue regeneration in the ovary, while concurrently inhibiting possibility of oncology relapse. In embodiments NK cells are injected as an adjuvant to stem cell and/or regenerative cell therapy to not only enhance therapeutic effect but also to reduce probability of tumor relapse.

Disclosed are compositions of matter, protocols and procedures useful for preventing/treatment ovarian failure. In one embodiment cytokines promoting anti-inflammatory/regenerative activity are administered systemically, or locally in order to preventing ovarian degeneration/fibrosis. In one embodiment low dose interleukin-2 is administered either alone or with adjuvant cytokines to induce an increase in FoxP3 expressing CD4 cells. In some embodiments in vivo generation of FoxP3 expressing CD4 cells is associated with stimulation of intra-ovarian angiogenesis and prevention of fibrosis.

Disclosed are means, methods and compositions of matter useful for quantifying the potency of regenerative therapeutics based on utilization of immunotherapies to induce tissue repair. In one embodiment said immunotherapy with regenerative activity is a T regulatory cell based therapy for stroke whose potency is quantified by assessment of one or more from the following: a) basal production of regenerative factors; b) induced production of regenerative factors; c) ability to prevent apoptosis of a target cell of interest; d) ability to stimulation proliferation of a target cell; and e) ability to induce proliferation of a progenitor cell belonging to tissue type of which therapy is desired.

Disclosed are means, methods and compositions of matter useful for prevention and/or reversion of type 1 diabetes by upregulation of myeloid suppressor cell activity in a mammal suffering from and/or at risk of developing type 1 diabetes. In one embodiment the invention teaches administration of immune cells that have been conditioned by exposure to regenerative cells, and/or cultured in the presence of factors produced from regenerative cells. In one embodiment said regenerative cells are umbilical cord derived mesenchymal stem cells. In one embodiment, immune cells that have been exposed to said regenerative cells are administered together with agents known to enhance myeloid suppressor cell activity. In another embodiment immune cells are administered together with exogenous myeloid suppressor cells.