The invention provides for transgenic donor animals (e.g., pigs) whose cells, tissues and organs have a better long-term survival when transplanted into a human patient. The transgenic donor animal carries one or more human transgenes which is expressed only when the endogenous gene of the donor animal is knocked out shortly before a graft is harvested for transplantation. This “genetic switch” allows the donor animal to remain healthy during the majority of its lifetime, while still allowing expression of the human transgene for optimal transplant tolerance in a human recipient. The transgene may encode a cytokine receptor, an adhesion molecule, or a complement regulatory protein.

Described herein are methods and systems for monitoring a disease state of a subject's bone marrow. Further, disclosed herein are methods and systems for monitoring a treatment state of a subject's organ. Moreover, disclosed herein are methods and systems for monitoring a healthy state of a subject's bone marrow and assaying an active agent.

A closed-system (i.e., hermetically sealed) methods, and kits for isolating Mesenchymal Stromal Cells (MSCs) from lipoaspirate, that utilizes specific hermetically-sealed, disposable assemblies and containers that are aseptically interconnected, are disclosed. Contemplated methods require lipoaspirate as a starting material, and provide for obtaining isolated, purified MSCs at the end of the process. Kits are contemplated to contain disposable assemblies, composed by sterile components such as modified syringes, tubing, centrifuge tubes, filtering units, that can be aseptically connected while maintaining sterility thereby keeping the system closed (i.e., hermetically sealed) with respect to the external environment. As a result, contamination during the isolation process can be avoided. The MSCs that are obtained at the end of the processing are thus ready to be further manipulated in subsequent operations (in example, expansion) also for therapeutic purposes.

Provided are hydrogel-based compositions and materials for wound healing and methods of using same. The hydrogel comprises nanofibers formed from protein Q, which is a variant of the cartilage oligomeric matrix protein coiled coil (COMPcc) protein, or a protein having at least 85% homology with protein Q. The hydrogel has one or more wound healing agents distributed therein and associated with the Q fibers. The wound healing agent may be exosomes, which may be exosomes produced by cells, such as exosomes produced by multipotent stromal cells and/or one or more triterpenoids. The hydrogels may be used in treatment of wounds, such as chronic wounds.

Methods and composition for production of T cells are provided. Also provided are therapeutic methods using engineered T cells. For example, in certain aspects methods include preparing three dimensional cell culture compositions comprising stroma cells and hematopoietic stem or progenitor cells in a serum-free medium for producing T cells.

Provided herein are methods and systems for recovering bone marrow. The methods comprising perfusing a bone with a perfusion media and recovering the liberated bone marrow cells.

Stromal stem cells are prospectively isolated from human bone marrow then expanded into clonal populations and cultured and used, the isolation being on the basis of expression of a cell surface marker, wherein the cell surface marker binds an antibody and wherein said antibody cross reacts with a cell surface marker found on mouse stromal stem cells or rat stromal stem cells, and optionally also on a cell of at least one other mammalian species selected from mouse, rat, horse, rabbit and pig cells. Useful stromal stem cell populations are positive for SDC2.

Inhibitor compounds and agents of Cathepsin C, CELA1, CELA3A and/or structurally related molecules thereto, compositions comprising same and uses thereof in the inhibition and/or prevention of cell and/or tissue necrosis is described. Various applications for the described compounds, and combination therapies are described as well.

A system and method of isolating extracellular vesicles. The method includes loading one or more of blood or bone marrow into an input port of a concentration system and centrifuging one or more of the blood or bone marrow to separate one or more of red blood cells, platelet poor plasma, or platelet rich plasma/bone marrow concentrate fractions via a centrifuge device. The method further includes pumping one or more of bone marrow/platelet rich plasma fractions and platelet poor plasma fractions into a receptacle of the concentration system and adding a concentrated aqueous two-phase solution to one or more of the bone marrow concentrate/platelet rich plasma fractions and platelet poor plasma fractions. The method also includes drawing the concentrated aqueous two-phase solution and one or more of the bone marrow concentrate/platelet rich plasma fractions or platelet poor plasma fractions back into the centrifuge device to isolate one or more of extracellular vesicles and platelet rich plasma/bone marrow concentrate fractions.

The invention relates to methods for determining the selectivity of a test compound and related methods such as methods for determining whether a subject suffering from cancer will respond or is responsive to treatment with a test compound or compositions comprising more than one test compound.