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Intervertebral disc degeneration (IVDD) is one of the main triggers of low back pain, which is most often associated with patient morbidity and high medical costs. IVDD triggers a wide range of pathologies and clinical syndromes like paresthesia, weakness of extremities, and intermittent/chronic back pain. Mesenchymal stem cells (MSCs) have demonstrated to possess immunomodulatory functions as well as the capability of differentiating into chondrocytes under appropriate microenvironment conditions, which makes them potentially epitome for intervertebral disc (IVD) regeneration. The IVD microenvironment is composed by niche of cells, and their chemical and physical milieus have been exhibited to have robust influence on MSC behavior as well as differentiation. Nevertheless, the contribution of MSCs to the IVD milieu conditions in healthy as well as degeneration situations is still a matter of debate. It is still not clear which factors, if any, are essential for effective and efficient MSC survival, proliferation, and differentiation. IVD microenvironment clues such as nucleopulpocytes, potential of hydrogen (pH), osmotic changes, glucose, hypoxia, apoptosis, pyroptosis, and hydrogels are capable of influencing the MSCs aimed for the treatment of IVDD. Therefore, clinical usage of MSCs ought to take into consideration these microenvironment clues during treatment. Alteration in these factors could function as prognostic indicators during the treatment of patients with IVDD using MSCs. Thus, standardized valves for these microenvironment clues are warranted.

Edifying the Focal Factors Influencing Mesenchymal Stem Cells by the Microenvironment of Intervertebral Disc Degeneration in Low Back Pain