The present invention relates to an indirect three-dimensional co-culture. The indirect co-culture may comprise bone marrow niche cells, tumor cells and a culture medium. The bone marrow niche cells and the tumor cells may be incubated in the culture medium without direct contact between the bone marrow niche cells and the tumor cells. The tumor cells may be dormant or reactivated. Also provided are a method for preparing the indirect co-culture and a method for screening for an agent capable of inhibiting reactivation of dormant tumor cells or promoting dormancy of proliferating tumor cells.

The present application relates to probiotic compositions, e.g., comprising at least one bacterial strain selected from: Streptococcus thermophiles, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, KE99, and Lactobacillus bulgaricus, optionally wherein the at least one bacterial strain is either alive or sonicated.

Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system. In some cases, the system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate.

Provided is a method of preparing a hydrogel composition including a uniform content of calcium phosphate, wherein a hydrogel composition prepared by the method has a uniform content of calcium phosphate, and thus may be used to quantify phosphates contained in the hydrogel composition. Provided is an in-vitro 3D osteoporosis model including a calcium phosphate hydrogel composition, wherein osteoblasts and osteoclasts may be three-dimensionally co-cultured inside a biogel, such that the osteoporosis model may be fabricated according to an intended use or clinical stage. Further, the model contains a calcium phosphate hydrogel with a uniform content of phosphate and thus enables quantification of calcium phosphate through measurement of phosphates, and therefore, the model may be used to screen candidate compounds for an osteoporosis drug and may effectively predict therapeutic effects of the drug on osteoporosis.

A simple, highly flexible and scalable platform for making functional complex tissues with heterogeneity and irregularity is provided. The method includes combining undifferentiated cells, such as pluripotent or multipotent stem cells, with a biomaterial to make multiple undifferentiated or naïve subunits, exposing the undifferentiated or naïve subunits to different cell culture environments for induction of differentiation towards different lineages as required by that complex tissue, and combining the then functional subunits with or without the undifferentiated subunits. The differentiated subunits thus combined can be cultured under biological, chemical, and/or physical culture conditions suitable to fine-tune the structural and functional properties of the bioengineered complex tissue to form a bioengineered tissue graft that mimics the structural and functional characteristics of native complex tissue. The bioengineered tissue graft can then used to replace dysfunctional tissue.

The present application relates to probiotic compositions, e.g., comprising at least one bacterial strain selected from: Streptococcus thermophiles, Bifidobacterium longum, Bifidobacterium breve, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, KE99, and Lactobacillus bulgaricus, optionally wherein the at least one bacterial strain is either alive or sonicated.

The described invention provides an ex vivo dynamic multiple myeloma cancer niche contained in a pumpless perfusion culture device. The dynamic multiple myeloma cancer niche includes (a) a three-dimensional tissue construct containing a dynamic ex vivo bone marrow niche, which contains a mineralized bone-like tissue containing viable osteoblasts self-organized into cohesive multiple cell layers and an extracellular matrix secreted by the viable adherent osteoblasts; and a microenvironment dynamically perfused by nutrients and dissolved gas molecules; and (b) human myeloma cells seeded from a biospecimen composition comprising mononuclear cells and the multiple myeloma cells. The human myeloma cells are in contact with osteoblasts of the bone marrow niche, and the viability of the human myeloma cells is maintained by the multiple myeloma cancer niche.

Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system. In some cases, the system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate.

Disclosed herein are various bioreactor devices and systems for growing cellular material, and related methods of growing cellular material. In some cases, a system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate. In some cases, a bioreactor can include an inner body which divides the bioreactor into several distinct chambers and facilitates the growth of a multi-tissue sample in the bioreactor. In some cases, a system can include a mechanical actuator situated to mechanically stress tissues grown in a bioreactor.

The present invention relates to compositions comprising induced T regulatory cells (iTregs), methods of making the compositions, and methods of using the compositions for enhancing bone remodeling in the treatment of Osteogenesis Imperfecta (OI).