Ex vivo human multiple myeloma cancer niche and its use as a model for personalized treatment of multiple myeloma

A method for preparing an ex vivo dynamic multiple myeloma (MM) cancer niche comprising

• a. acquiring a biospecimen containing mononuclear cells from a subject in need thereof, wherein the biospecimen comprises viable multiple myeloma cells;
• b. preparing a biospecimen composition comprising the viable multiple myeloma cells and plasma autologous to the subject;
• c. preparing a three-dimensional tissue construct containing a dynamic ex vivo bone marrow (BM) niche comprising
• (i) a mineralized bone-like tissue comprising (a) viable osteoblasts self-organized into cohesive multiple cell layers and (b) an extracellular matrix secreted by the viable adherent osteoblasts;
• and
• (ii) a microenvironment dynamically perfused by nutrients and dissolved gas molecules;
• d. adding the biospecimen composition to the three-dimensional tissue construct containing the dynamic ex vivo bone marrow (BM) niche to seed the BM niche with MM cells;
• e. forming the dynamic ex vivo MM niche such that the MM cells are in contact with the osteoblasts of the BM niche, wherein the MM cancer niche is capable of maintaining viability of the human myeloma cells.

A method for assessing chemotherapeutic efficacy of a chemotherapeutic agent on viable human multiple myeloma cells obtained from a subject comprising:

• a. acquiring a biospecimen from the subject, wherein the biospecimen comprises viable multiple myeloma cells;
• b. preparing a biospecimen composition comprising the viable multiple myeloma cells and plasma autologous to the subject;
• c. preparing a three-dimensional tissue construct containing a dynamic ex vivo bone marrow (BM) niche comprising
• (i) a mineralized bone-like tissue comprising (a) viable osteoblasts self-organized into cohesive multiple cell layers and (b) an extracellular matrix secreted by the viable adherent osteoblasts;
• and
• (ii) a microenvironment dynamically perfused by nutrients and dissolved gas molecules;
• d. adding the biospecimen composition to the three-dimensional tissue construct containing the dynamic ex vivo bone marrow (BM) niche to seed the BM niche with MM cells;
• e. forming the dynamic ex vivo MM niche such that the MM cells are in contact with the osteoblasts of the BM niche,
• wherein the MM cancer niche is capable of maintaining viability of the human myeloma cells;
• f. optionally cultivating the human myeloma cells in the MM cancer niche to propagate the MM cells for a period of time;
• g. adding a test chemotherapeutic agent to the dynamic ex vivo MM niche comprising viable human myeloma cells;
• h. comparing at least one of viability and level of apoptosis of the MM cells in the MM niche in the presence of the chemotherapeutic agent to an untreated control;
• and
• i. initiating therapy to treat the MM in the patient if the agent significantly reduces viability or increases apoptosis of the MM cells.