Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc

Abstract

BackgroundHuman adipose-derived mesenchymal stem cells (ADMSCs) may be ideal source of cells for intervertebral disc (IVD) regeneration, but the harsh chemical microenvironment of IVD may significantly influence the biological and metabolic vitality of ADMSCs and impair their repair potential. This study aimed to investigate the viability, proliferation and the expression of main matrix proteins of ADMSCs in the chemical microenvironment of IVD under normal and degeneration conditions.MethodsADMSCs were harvested from young (aged 8-12 years, n = 6) and mature (aged 33-42 years, n = 6) male donors and cultured under standard condition and IVD-like conditions (low glucose, acidity, high osmolarity, and combined conditions) for 2 weeks. Cell viability was measured by annexin V-FITC and PI staining and cell proliferation was measured by MTT assay. The expression of aggrecan and collagen-I was detected by real-time quantitative polymerase chain reaction and Western blot analysis.ResultsIVD-like glucose condition slightly inhibited cell viability, but increased the expression of aggrecan. In contrast, IVD-like osmolarity, acidity and the combined conditions inhibited cell viability and proliferation and the expression of aggrecan and collagen-I. ADMSCs from young and mature donors exhibited similar responses to the chemical microenvironments of IVD.ConclusionIVD-like low glucose is a positive factor but IVD-like high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of ADMSCs. These findings may promote the translational research of ADMSCs in IVD regeneration for the treatment of low back pain.

The potential of chondrogenic pre-differentiation of adipose-derived mesenchymal stem cells for regeneration in harsh nucleus pulposus microenvironment

“…8,15,16 However, the microenvironment condition in degenerated disc is characterized of hypoxia, low nutrition, acidic pH, high mechanical loading, high osmolarity, and a complicated protease and cytokine network. 1,4,6,12 It is quite different from normal disc and may have negative impact to graft cells. It is reported that 60% of bovine BM-MSCs survived after initial injection in to a cryopreserved IVD tissue in vitro, but only 20% of cells remained alive after seven days.…”

“…Despite the IVD-like glucose condition was found a positive factor for ADSCsbased IVD regeneration, the cell viability and proliferation and the matrix biosynthesis capability were inhibited in combined IVD condition. 4,19,20 From this respect, the IVD condition is still an obstacle for the application of cell-based therapy to treat degenerative diseases.…”

“…The degenerated disc is characterized as reduction in cell viability, loss of NP cells, loss of proteoglycan, development of NP dehydration, and accumulation of waste products. 4,5 To repair the disc degeneration, researchers have been utilizing cell-based therapies, which turn out to be a possible approach from animal trials and clinical reports. Researchers found increased magnetic resonance imaging (MRI) T2 signal and preservation of disc height in discs received cell therapy.…”

“…The condition in degenerated disc is characterized by low oxygen tension, limited nutrition, acidic pH, and high osmolarity, which may negatively influence the function or even survival of any implanted cells. 4,6,[12][13][14] To overcome harsh condition in disc, previous literatures proposed pre-conditioning cells before implantation 6 and appropriately differentiated cells could survive and synthesize matrix in situ. 10 With this in mind, we designed this study to investigate the potential effect of chondrogenic pre-differentiation on the regeneration of adipose-derived mesenchymal stem cells (ADSCs) in a harsh IVD-like condition.…”

Comparison of biological characteristics of nucleus pulposus mesenchymal stem cells derived from non-degenerative and degenerative human nucleus pulposus

“…Numerous stem cell types have been used in the field of cell transplantation for the treatment of IDD, such as bone marrow-derived stem cells (BMSCs) (10), adipose-derived MSCs (ADMSCs) (11), human umbilical tissue-derived cells (12) and synovium-derived stem cells (13 (14,15). Certain studies have reported that these stem cells lack viability, proliferation and matrix biosynthesis under conditions resembling the IVD microenvironment, which negatively influences the biological and metabolic vitality of stem cells and impairs their repair potential (16,17). In recent years, increasing evidence supported the existence of nucleus pulposus MSCs (NPMSCs) in the nucleus pulposus (18)(19)(20)(21)(22)(23)(24).…”