Therapeutic Solutions International, Inc.

Spinalcyte, LLC

Figene, LLC

Other

Creative Medical Technologies, Inc.

Aethlon Medical, Inc.

Regen Biopharma, Inc.

Creative Medical Health, Inc.

Xon Cells, Inc.

Nobilis Therapeutics, Inc.

Viera Bioscience, Inc.

Harrow Ip, LLC

Zander Therapeutics, Inc.

Kcl Therapeutics, Inc.

Stemspine LLC

Thomas E Ichim

Pete O'Heeron

David Koos

Timothy G Dixon

Vlad Bogin

James Veltmeyer

Santosh Kesari

Amit N Patel

Richard H Tullis

Famela Ramos

Amit Patel

Kristin Comella

Vladimir Bogin

Kalina O'Connor

Dennis Elias Saadeh

Harry M Lander

Annette Marleau

Neil Riordan

Fabio Salazar

Boris N Reznik

Christopher J Dougherty

Feng Lin

Wais Kaihani

Gerry B Berg

Robert F Graham

In some aspects, disclosed herein are methods and compositions for treatment or prevention of cerebral palsy using fibroblasts or derivatives thereof. Disclosed herein are fibroblasts and derivatives thereof capable of inducing neurogenesis and/or reducing inflammation in a subject. In some cases, the disclosed methods comprise use of conditioned fibroblasts. Fibroblasts may be conditioned with agents capable of enhancing therapeutic efficacy, for example oxytocin and/or human chorionic gonadotrophin (hCG).

Treatment of cerebral palsy using fibroblasts

Embodiments of the disclosure include methods and compositions related to prevention of spontaneous miscarriage in an individual. In certain cases, fibroblasts are provided in an effective amount to an individual in need thereof. Alternatively or in addition, lymphocytes are obtained, cultured with fibroblasts, and provided to an individual. Fibroblasts may modulate an immune response in an individual, thereby reducing the risk of spontaneous miscarriage.

Prevention of recurrent miscarriages through administration of fibroblasts and fibroblast-educated paternal cells

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.

Prevention and/or treatment of type 1 diabetes by augmentation of myeloid suppressor cell activity

Disclosed are methods, means and compositions of matter useful for treatment of heart failure, and/or post infarct pathological remodeling using ex vivo reprogrammed immune cells. In one embodiment, cells of the recipient (autologous) are cocultured with a regenerative cell population alone or in the presence of one or more adjuvants. Said adjuvants enhance transfer of regenerative activity from said mesenchymal stem cells to said immune cells. In one embodiment said ex vivo reprogrammed immune cells are capable of inducing death or inactivation of cardiac fibrotic cells. In other embodiments, said immune cells provide antifibrotic activity to induce suppression of cardiac fibrosis. In other embodiments, said immune cells provide for growth factors to enhance cardiac regeneration.

Treatment of heart failure and/or post infarct pathological remodeling by ex vivo reprogrammed immune cells

Disclosed are methods, means, and compositions of matter useful for the stimulation of angiogenesis directly by administration of membrane vesicles, such as fibroblast-derived exosomes, and/or through induction of angiogenic cytokines from blood cells contacted with fibroblast-derived exosomes. The invention provides means of treating conditions in which angiogenesis is beneficial through local or systemic administration of exosomes, including those derived from fibroblasts, wherein the fibroblasts are cultured under basal conditions or conditions of hypoxia. In other embodiments exosomes derived from fibroblasts are utilized to augment endogenous regenerative processes, such as hematopoiesis, angiogenesis and neurogenesis, as well as augment regenerative processes stimulated by administration of exogenous therapeutics such as cells, growth factors, or genes.

Stimulation of angiogenesis by fibroblast derived exosomes

The present disclosure is directed to systems, methods, and compositions for functional interaction of fibroblasts with one or more types of immune cells such that the interaction results in modification to the fibroblasts, the one or more types of immune cells, or both. In some embodiments, one or more certain agents are also utilized during the interaction or in lieu of one of the types of cells. In specific embodiments, cells to be used in cellular transplantation therapy are modified to have reduced immunogenicity.

Interaction of fibroblasts and immune cells for activation and uses thereof

Disclosed are methods and compositions comprising fibroblasts and/or products derived thereof for the inhibition and/or treatment of addiction of any kind, such as opioid addiction. In some embodiments, methods comprise treating a patient addicted to opioids by administering a fibroblast population at a concentration sufficient for suppression of addiction-associated brain damage. In some embodiments, the fibroblasts express CD31 and/or CD73 markers. In some embodiments, fibroblasts are used to endow neuronal regeneration in order to overcome changes in the brain associated with addiction. Some embodiments relate to the stimulation of hippocampal regeneration subsequent to addiction induced damage.

Treatment of opioid addiction using fibroblasts and products thereof

Disclosed are compositions and methods of treating muscular dystrophies, including Duchenne Muscular Dystrophy (DMD) through administration of fibroblasts and modified fibroblasts systemically and locally. In certain embodiments, fibroblast cells are utilized for replacement of dystrophin through fusion and/or other means of horizontal gene transfer. In other embodiments, the disclosure teaches the use of fibroblasts for reduction of inflammatory reactions and/or immunological reactions which propagate and enhance myodestructive aspects of Duchenne Muscular Dystrophy. In other embodiments, fibroblasts are utilized as vectors for gene therapy and/or gene modifications approaches.

Fibroblast therapy for treatment of Duchenne muscular dystrophy

Disclosed are novel means of enhancing mesenchymal stem cell regenerative activities including, intra alia, production from pulmonary leakage and suppression of scar tissue formation by co-administration with T regulatory cells. In some embodiments the invention provides an interaction between T regulatory cells and mesenchymal stem cells in which T regulatory cells stimulate upregulation of mesenchymal stem cell activity in a GITR dependent manner.

Stimulation of mesenchymal stem cell therapeutic activities by T regulatory cells

Embodiments of the disclosure include methods and compositions for treatment of lung disease, including at least chronic obstructive pulmonary disease (COPD). In particular cases, fibroblasts (including activated fibroblasts) and/or exosomes thereof are provided to an individual for the treatment of COPD. In particular cases the fibroblasts are activated and/or express one or more particular markers.

Treatment of chronic obstructive pulmonary disease and lung degeneration using activated fibroblasts and exosome derivatives thereof

Embodiments of the disclosure include methods and compositions for use of prepared fibroblasts and/or conditioned media therefrom. In particular embodiments, the prepared fibroblasts have enhanced regenerative and may have an increase in secretion of one or more cytokines and/or growth factors; may have an increase in anti-apoptotic activity; and/or may have a modulated immunogenicity. In specific embodiments, the fibroblasts are prepared by exposure to hypoxia and/or carbon monoxide.

Augmentation of fibroblast regenerative activity

Disclosed are means, methods, and therapeutic compositions for prevention of memory loss during situations of neuroinflammation. In one embodiment the invention teaches administration of the therapeutic combination of ingredients comprising of pterostilbene,, sulforaphane, and epigallocatechin-3-gallate (EGCG) to a mammal suffering from inflammation in order to preserver memory function.

Prevention of neuroinflammation associated memory loss using nutraceutical compositions

Disclosed are means, compounds, and compositions of matter useful for stimulation of natural killer cell activity. On one embodiment a composition termed QuadraMune™ comprised of pterostilbene,extract, green tea extract, and broccoli. In some embodiments the invention teaches the administration of a therapeutic combination of ingredients comprising of metformin, pterostilbene,, sulforaphane, and epigallocatechin-3-gallate (EGCG) to a mammal in need of natural killer cell immune modulation. In another embodiment, the invention teaches administration of said therapeutic combination to a mammal infected with said SARS-CoV-2. In some embodiments dosage of said therapeutic combination is based on inflammatory and/or immunological parameters observed in patients with COVID-19.

Stimulation of NK cell activity by using a combination of broccoli, Nigella Sativa, Green Tea, and pterostilbene alone and together with metformin

Described are means, methods, and compositions useful for treatment of multiple sclerosis through the utilization of fibroblasts and/or derivatives thereof to concurrently stimulate regenerative processes while inducing a protolerogenic immune modulatory program. In certain embodiments, fibroblasts are selected for the concurrent properties of immune modulation and regeneration by enrichment for CD73 expressing fibroblasts. In particular embodiments, stimulation of regeneration implies activation of endogenous neural progenitor cells. In some embodiments, stimulation of regeneration implies induction of remyelination. The utilization of fibroblasts as a superior source for immune modulation, prevention of immune mediated pathology, and activation of T regulatory cells is provided within the context of multiple sclerosis.

Concurrent activation of regenerative and tolerogenic processes by fibroblast-based compositions for the treatment of multiple sclerosis

Disclosed are means, methods, and compositions of matter useful for treatment of neuroinflammation, autoimmunity, transplant rejection, or graft versus host disease (GVHD) comprising exposing autologous immune cells to allogeneic amniotic fluid derived stem cells. In one embodiment peripheral blood mononuclear cells are cultured in the presence of amniotic fluid stem cells in the presence of interleukin-2 for a period of time sufficient to endow tolerogenic properties. Said tolerogenic properties include ability to suppress adaptive or innate immune responses. In another embodiment the invention provides methods of generating antigen specific immune regulatory cells by culture of lymphocytes together with amniotic fluid stem cells in the presence of antigen to which specific immune regulation is desired.

Growing community of inventors

Oceanside, CA, United States of America

Thomas E Ichim