A mesenchymal stem cell harvesting system and method for increasing the efficiency of collecting and processing physiological fluids containing mesenchymal stem cells from a cavity within a patient’s skeletal system. Microenvironments risk in MSC production and concentration within a cavity, for example the patient’s ilium, are penetrated with a pointed instrument used to create an aperture in the hard cortical bone forming the cavity followed by the insertion of an aspiration device which extracts one or more samples of cancellous bone, bone marrow, bone marrow blood and other aspirated material. The aspirate is rinsed and may be filtered to remove unwanted material and to increase the concentration and purity of the mesenchymal stem cells in the aspirant far beyond levels formerly obtainable for use in autologous treatment of the patient.

Disclosed herein is a novel chimeric antigen receptor and use thereof. The novel chimeric antigen receptor consists of a signal peptide, an antigen binding domain, a transmembrane region, and an intracellular signal domain, and comprises a 4-1BB signal peptide and/or a 4-1BB molecular transmembrane region. Nucleic acid sequences of various chimeric antigen receptors are separated and purified and provided is a chimeric antigen receptor and a CAR-T cell which are specific for a CD19 malignant tumor antigen. In the malignant tumor killing test of hematological cell lines, the ability of immune cells to target and recognize tumor cells is significantly enhanced, and the killing activity against tumor cells is also enhanced.

The present invention provides preparations of MSCs with important therapeutic potential. The MSC cells are non-primary cells with an antigen profile comprising less than about 1.25% CD45+ cells (or less than about 0.75% CD45+), at least about 95% CD105+ cells, and at least about 95% CD166+ cells. Optionally, MSCs of the present preparations are isogenic and can be expanded ex vivo and cryopreserved and thawed, yet maintain a stable and uniform phenotype. Methods are taught here of expanding these MSCs to produce a clinical scale therapeutic preparations and medical uses thereof.

Described are embodiments for expanding cells in a bioreactor. In one embodiment, methods are provided that distribute cells throughout the bioreactor and attach cells to specific portions of a bioreactor to improve the expansion of the cells in the bioreactor. Embodiments may be implemented on a cell expansion system configured to load, distribute, attach and expand cells.

It is intended to provide MSCs for transplantation that have an improved post-transplantation cell survival rate and engraftment rate and are highly safe with fewer adverse reactions, and a method for conveniently producing MSCs for transplantation having a high cell survival rate and engraftment rate. As means therefor, the present invention provides a stem cell for transplantation comprising an MSC capable of overexpressing IL-10.

A method for treating a subject having a medical condition associated with inflammation and/or an unwanted immune response without an alpha1-antitrypsin (AAT) deficiency, wherein the method comprises administering genetically modified mesenchymal stem cells to the subject, wherein said genetically modified mesenchymal stem cells comprise an exogenous nucleic acid comprising (i) an Alpha-1 antitrypsin (AAT) encoding region operably linked to (ii) a promoter or promoter/enhancer combination.

This disclosure relates to methods of preserving mesenchymal stromal/stem cells (MSCs) for use in clinical applications. In certain embodiments, this disclosure relates to methods of preserving MSCs comprising mixing MSCs with interferon-gamma prior to cryopreserving, freezing, or cooling the MSCs to a temperature below zero degrees Celsius.

Methods of treating an ischemic disease in a subject are provided. Accordingly there is provided a method comprising administering to the subject a therapeutically effective amount of cells with reduced level of expression and/or activity of TNFR1, thereby treating the ischemic disease in the subject. Also provided is a method comprising treating with TNFalpha cells with reduced expression and/or activity of TNFR1 and administering to the subject a therapeutically effective amount of said cells, thereby treating the ischemic disease in the subject.

Provided are methods for treating a disease using bioengineered enucleated cells. Also provided herein are compositions comprising enucleated cells, wherein the enucleated cells have been loaded with clinically relevant biomolecules.

Accordingly. the present disclosure provides a population of genetically engineered mesenchymal stem cells (MSCs), comprising an expression vector comprising an Akt or HGF gene and a PD-L1 gene. Also provided is a method for synergistically increasing survival status and immunomodulatory ability of an MSC or enhancing proliferation of an MSC, comprising transfecting an MSC with an Akt or HGF gene and a PD-L1 gene and a method for preventing, ameliorating and/or treating an ischemia condition, enhancing neuroregeneration or reducing neuronal death, comprising administering an effective amount of a population of genetically engineered MSCs of the present disclosure to a subject in need thereof.