The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.

The described invention identifies endothelial cells within the perivascular niche as a crucial component in driving bone marrow (BM) inflammation and HSC dysfunction. We demonstrate that crosstalk between ERK-MAPK and NF-κB signaling pathways within the endothelium plays a key role in modulating the outcomes of chronic inflammation. Sustained activation of the MAPK pathway selectively within the endothelium of adult mice leads to inflammation-induced HSC dysfunction including loss of engraftment ability and a myeloid-biased output. HSC defects caused by endothelial MAPK activation are completely resolved upon simultaneous inhibition of endothelial NF-κB signaling. The described invention identifies Stem Cell Growth Factor alpha (SCGF) as a niche-derived factor that suppresses BM inflammation and enhances hematopoietic recovery following myelosuppressive injury.

The present invention provides a recombinant exosome comprising a membrane-bound EGF protein on the surface of the recombinant exosome and provides a use of the recombinant exosome.

The present invention provides a recombinant exosome comprising a membrane-bound EGF protein on the surface of the recombinant exosome and provides a use of the recombinant exosome.

The present disclosure relates to heterogeneous cell compositions derived from canine or feline uterine tissue and methods of producing and use thereof. In some aspects, the heterogeneous cell compositions comprise a mixture of mesenchymal progenitor cells and epithelial progenitor cells. In some aspects, the heterogeneous cell compositions are used as an autologous or allogeneic treatment for the treatment of diseases such as chronic kidney disease, atopic dermatitis, immune mediated arthritis, hepatitis, liver disease, inflammatory bowel disease, osteoarthritis, intravertebral disc disease, keratoconjunctivitis sicca (dry eye), pancreatitis, fibrosis, sclerosis, amyloidosis, immune mediated polyarthritis or wounds in canines and felines.

The present disclosure relates to heterogeneous cell compositions derived from canine or feline uterine tissue and methods of producing and use thereof. In some aspects, the heterogeneous cell compositions comprise a mixture of mesenchymal progenitor cells and epithelial progenitor cells. In some aspects, the heterogeneous cell compositions are used as an autologous or allogeneic treatment for the treatment of diseases such as chronic kidney disease, atopic dermatitis, immune mediated arthritis, hepatitis, liver disease, inflammatory bowel disease, osteoarthritis, intravertebral disc disease, keratoconjunctivitis sicca (dry eye), pancreatitis, fibrosis, sclerosis, amyloidosis, immune mediated polyarthritis or wounds in canines and felines.

Compositions comprising donor cells, acceptor cells, membrane-enclosed bodies and methods are described herein.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.

Embodiments herein relate to in vitro production methods of hematopoietic stem cell (HSC) and hematopoietic stem and progenitor cell (HSPC) that have long-term multilineage hematopoiesis potentials upon in vivo engraftment. The HSC and HSPCs are derived from pluripotent stem cells-derived hemogenic endothelia cells (HE) by non-integrative episomal vectors-based gene transfer.