MAPC therapeutics without adjunctive immunosuppressive treatment
Inventors
Mays, Robert W. • Deans, Robert J.
Assignees
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Publication Number
US-11992507-B2
Publication Date
2024-05-28
Expiration Date
Abstract
The invention relates to the treatment of various injuries, disorders, dysfunctions, diseases, and the like with MAPCs, without the need for adjunctive immunosuppressive treatment.
Core Innovation
The invention relates to a method of administering expanded multipotent stem cells to a subject. The expanded multipotent stem cells are not embryonic stem cells, embryonic germ cells, or germ cells, and can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages. The cells express telomerase and are allogeneic or xenogeneic to the subject, yet are not immunogenic to the subject.
The method further requires that the cells have undergone at least 10 to 40 cell doublings in culture and are administered without also administering an immunosuppressive treatment to the subject adjunctively to said cells. The cells are derived from bone marrow and have not been genetically engineered to improve their immunomodulatory properties.
The described approach is grounded in the immunogenicity rationale that the expanded multipotent stem cells are weakly non-immunogenic or non-immunogenic to the subject and are intended to avoid concerns such as graft rejection and teratoma. The method also specifies explicit exclusions that the cells are not administered to ameliorate a brain injury caused by hypoxia, and excludes use as adjunctive treatment of an immune dysfunction characterized by adverse T-cell activation or proliferation, as well as treating diabetes, suppressing graft versus host disease, ameliorating an immune dysfunction, and treating multiple sclerosis.
Claims Coverage
The document includes one independent claim. The independent claim centers on administering expanded multipotent stem cells that are non-embryonic and multilineage differentiating, telomerase-expressing, allogeneic or xenogeneic but non-immunogenic, after defined cell doublings, and doing so without adjunctive immunosuppressive treatment, with additional explicit exclusions of specified treatment indications.
Non-embryonic expanded multipotent stem cells with multilineage differentiation
Administering to a subject expanded multipotent stem cells that are not embryonic stem cells, embryonic germ cells, or germ cells, and that can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages.
Telomerase-expressing allogeneic or xenogeneic cells that are not immunogenic
Using expanded multipotent stem cells that express telomerase, are allogeneic or xenogeneic to the subject, and are not immunogenic to the subject.
Cultured cell doublings without adjunctive immunosuppressive treatment
Administering cells that have undergone at least 10 to 40 cell doublings in culture without also administering an immunosuppressive treatment to the subject adjunctively to said cells.
Bone marrow-derived non-genetically engineered immunomodulatory profile
Administering cells that are derived from bone marrow and have not been genetically engineered to improve their immunomodulatory properties.
Explicit exclusion of specified treatment indications
Administering the cells with the condition that the cells are not administered to ameliorate a brain injury caused by hypoxia, and with further conditions that the cells are not administered as adjunctive treatment of an immune dysfunction characterized by adverse T-cell activation or proliferation, not administered to treat diabetes, not administered to suppress graft versus host disease, not administered to ameliorate an immune dysfunction, and not administered to treat multiple sclerosis.
Across the independent claim, the inventive core is the combination of multilineage, non-embryonic expanded multipotent stem cells that express telomerase and are allogeneic or xenogeneic yet not immunogenic, cultured through defined cell doublings, derived from bone marrow and not genetically engineered for immunomodulatory improvement, administered without adjunctive immunosuppressive treatment, while explicitly excluding certain treatment indications.
Stated Advantages
Avoidance of administering an immunosuppressive treatment adjunctively to the administered cells.
Cells are not immunogenic to the subject, with an immunogenicity rationale described as weakly non-immunogenic or non-immunogenic.
Explicit avoidance of concerns such as teratoma and graft rejection are referenced in the described rationale.
Documented Applications
Treatment-related context including rat hypoxic-ischemic brain injury and surgical ischemic stroke models, with behavioral improvements and findings including engraftment/persistence, neuronal protection, and differentiation marker expression as described.
Use-case framing of excluded indications is provided for brain injury caused by hypoxia, immune dysfunction characterized by adverse T-cell activation or proliferation, diabetes, graft versus host disease, immune dysfunction generally, and multiple sclerosis.
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