Compositions and methods for treating and preventing tissue injury and disease
Inventors
Peterson, Dale R. • Mattern, Ralph-Heiko • WILSON-WIRTH, I, Cory • Ohashi, Kevin L.
Assignees
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Publication Number
US-9872937-B2
Publication Date
2018-01-23
Expiration Date
Abstract
The present invention provides novel compositions comprising multipotent cells or microvascular tissue, wherein the cells or tissue has been sterilized and/or treated to inactivated viruses, and related methods of using these compositions to treat or prevent tissue injury or disease in an allogeneic subject.
Core Innovation
A composition comprising processed microvascular tissue is described, wherein the processed microvascular tissue comprises isolated, uncultured multipotent cells. The composition is sterilized by irradiation and is characterized by one or more of angiogenic activity or anti-inflammatory activity greater than saline alone, while less than or equal to 50% of the cells present in the composition are viable.
The document describes allogeneic and xenogeneic treatment of tissue injury using sterilized and/or virus-inactivated, minimally processed uncultured multipotent cells and/or processed microvascular tissue, including cell membranes and ECM components. Angiogenic and anti-inflammatory activity is described as retained after sterilization by irradiation and after preservation formats including dried, lyophilized, or cryopreserved states.
The compositions are described as intentionally low viability, including substantially non-viable preparations and optionally trypan-blue-excluding populations. The document also describes optional preservation and formulation aspects such as moisture-impermeable containers and room-temperature stability for at least 1 month, and optionally includes implantable scaffolds or matrices for tissue repair.
The background and supporting rationale emphasize that the sterilized and minimally processed multipotent cell or microvascular tissue compositions can provide angiogenic and anti-inflammatory activity despite low viability, while also addressing sterility and reducing immune response and rejection risk in allogeneic or xenogeneic use.
Claims Coverage
The independent claim provides a composition centered on processed microvascular tissue with isolated, uncultured multipotent cells sterilized by irradiation, while retaining angiogenic and/or anti-inflammatory activity relative to saline and limiting cell viability. Dependent claims further refine the composition with route of administration, viability limits, irradiation dose, trypan-blue-excluding populations, and optional scaffold content.
Processed microvascular tissue with isolated, uncultured multipotent cells
The composition comprises processed microvascular tissue wherein the processed microvascular tissue comprises isolated, uncultured multipotent cells.
Irradiation sterilization of the composition
The composition is sterilized by irradiation.
Angiogenic or anti-inflammatory activity greater than saline alone
The composition has one or more of angiogenic activity or anti-inflammatory activity greater than saline alone.
Viability-limited cell population
Less than or equal to 50% of the cells present in the composition are viable.
Intravenous administration
The composition is formulated for intravenous administration.
Irradiation dose threshold greater than 0.5 Mrad
The composition is irradiated at a dose greater than 0.5 Mrad.
No more than 10% viable cells
The composition has no more than 10% viable cells among the cells present.
Trypan-blue-excluding viability criterion
At least 1% of the cells exclude trypan blue.
Implantable scaffold or matrix
The composition further includes an implantable scaffold or matrix.
Across the independent claim and dependent refinements, the coverage is directed to sterilized processed microvascular tissue comprising isolated, uncultured multipotent cells, retaining angiogenic and/or anti-inflammatory activity greater than saline, while constraining viability to ≤50% (and optionally ≤10% or trypan-blue-excluding populations) and optionally specifying intravenous administration and inclusion of an implantable scaffold or matrix.
Stated Advantages
Angiogenic and/or anti-inflammatory activity greater than saline alone is maintained in the sterilized composition.
Sterility is addressed via sterilization by irradiation.
Reduced immune response and rejection risk is described for allogeneic and xenogeneic use.
Activity is described as retained after sterilization and preservation formats despite low viability, including substantially non-viable preparations.
Documented Applications
Allogeneic and xenogeneic treatment of tissue injury.
Restoration of perfusion in a hindlimb ischemia model.
Repair of Achilles tendon injury.
Repair in rheumatoid arthritis model.
Repair of bone, cartilage, and meniscal defects.
Treatment or testing of angiogenic and anti-inflammatory effects using endothelial migration/chemoattraction, microvesicle uptake, and vessel formation assays.
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