Adherent cells from placenta and use of same in disease treatment
Inventors
Assignees
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Publication Number
US-10610545-B2
Publication Date
2020-04-07
Expiration Date
Abstract
Methods for treating conditions by administration of placenta derived adherent stromal cells to a subject in thereof are provided. Such conditions include skeletal muscle defects, neuropathic pain, and myocardial infarction. Also provided are methods wherein the adherent stromal cells administered are cultured under 2 dimensional or 3 dimensional growth conditions. Also provided are methods in which the cells administered are at least 70% adherent cells from a maternal or fetal portion of the placenta.
Core Innovation
The disclosure relates to placenta-derived adherent stromal (mesenchymal) cells and conditioned media for treating multiple diseases. The described cell populations are purified adherent populations enriched for a maternal portion of the placenta and are characterized by positive and negative immunophenotypic marker profiles, including cells that express one or more markers selected from CD73, CD90, CD29, CD105, or D7-fib and cells that do not express a defined list of markers including CD3, CD4, CD45, CD80, HLA-DR, CD11b, CD14, CD19, CD34, CD31, CD200, KDR, or CD79.
A key aspect is the defined differentiation and functional behavior of the maternal portion-derived adherent cells. Relative to bone-marrow adherent cells under inducing conditions, the placental adherent cells show reduced osteogenic commitment and reduced adipogenic commitment, including reduced differentiation into osteogenic lineages and reduced differentiation into adipogenic lineages. The disclosure also describes immunomodulation, including T-cell suppression in a mixed lymphocyte culture context, and conditioned-medium effects, including pro-angiogenic effects on HUVEC.
The disclosure connects these maternal portion-derived placental adherent cells to specific in vivo applications including skeletal muscle crush regeneration and inflammatory pain and neuropathic pain models. It further describes opioid peptide content in PLX, including beta-endorphin, dynorphin A, leu-enkephalin, and met-enkephalin, and reports effects in these pain models together with additional animal model descriptions including a myocardial infarction and VAD-related mouse model.
Claims Coverage
The provided portion includes two independent methods that both administer a placenta-derived adherent cell population comprising adherent cells from a maternal portion of the placenta. Across these independent claims, the inventive features include the trauma context and the cell origin, with dependent claims adding specific marker, differentiation-propensity, and opioid-peptide-related refinements.
Treating skeletal muscle trauma caused directly by physical injury using placental maternal adherent cells
A method of treating skeletal muscle trauma resulting directly from a physical injury in a subject in need thereof by administering a composition comprising a population of adherent cells derived from a placenta, wherein the population comprises adherent cells from a maternal portion of the placenta, thereby treating the skeletal muscle trauma.
Treating skeletal muscle trauma not resulting directly from ischemia using placental maternal adherent cells
A method of treating skeletal muscle trauma in a subject in need thereof by administering a composition comprising a population of adherent cells derived from a placenta, wherein the population comprises adherent cells from a maternal portion of the placenta, and wherein said skeletal muscle trauma does not result directly from ischemia, thereby treating the skeletal muscle trauma.
Overall, the claim set portion focuses on treating skeletal muscle trauma in a subject by administering a placenta-derived adherent cell composition enriched for adherent cells from the maternal portion of the placenta, with claim differentiation based on whether the trauma results directly from physical injury or does not result directly from ischemia. Dependent refinements specify negative and positive immunophenotypic marker expression, reduced or absent osteogenic and adipogenic differentiation relative to bone-marrow-derived cells under inducing conditions, and expression of named opioid peptides.
Stated Advantages
Immunomodulation/T-cell suppression in mixed lymphocyte culture.
Conditioned-medium pro-angiogenic effects on HUVEC.
Reduced osteogenic commitment and reduced adipogenic commitment compared with bone-marrow adherent cells.
Effects in vivo on skeletal muscle crush regeneration.
Effects in inflammatory pain and neuropathic pain models.
Presence of opioid peptides in PLX including beta-endorphin, dynorphin A, leu-enkephalin, and met-enkephalin.
Documented Applications
Treating skeletal muscle trauma resulting directly from a physical injury, including skeletal muscle crush regeneration.
Treating inflammatory pain (Freund’s adjuvant inflammatory pain model).
Treating neuropathic pain (CCI neuropathic pain model).
Myocardial infarction/VAD-related mouse model efficacy described in connection with the disclosure.
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