The role of microenvironment in stem cell-based regeneration of intervertebral disc

Abstract

Regenerative medicine for intervertebral disc (IVD) disease, by utilizing chondrocytes, IVD cells, and stem cells, has progressed to clinical trials in the treatment of back pain, and has been studied in various animal models of disc degeneration in the past decade. Stem cells exist in their natural microenvironment, which provides vital dynamic physical and chemical signals for their survival, proliferation and function. Long-term survival, function and fate of mesenchymal stem cells (MSCs) depend on the microenvironment in which they are transplanted. However, the transplanted MSCs and the endogenous disc cells were influenced by the complicated microenvironment in the degenerating disc with the changes of biochemical and biophysical components. It is important to understand how the MSCs and endogenous disc cells survive and thrive in the harsh microenvironment of the degenerative disc. Furthermore, materials containing stem cells and their natural microenvironment have good clinical effects. However, the implantation of tissue engineering IVD (TE-IVD) cannot provide a complete and dynamic microenvironment for MSCs. IVD graft substitutes may need further improvement to provide the best engineered MSC microenvironment. Additionally, the IVD progenitor cells inside the stem cell niches have been regarded as popular graft cells for IVD regeneration. However, it is still unclear whether actual IVD progenitor cells exist in degenerative spinal conditions. Therefore, the purpose of this review is fourfold: to discuss the presence of endogenous stem cells; to review and summarize the effects of the microenvironment in biological characteristics of MSC, especially those from IVD; to explore the feasibility and prospects of IVD graft substitutes and to elaborate state of the art in the use of MSC transplantation for IVD degeneration in vivo as well as their clinical application.

RETRACTED ARTICLE: Future of low back pain: unravelling IVD components and MSCs’ potential

“…MSCs can either be obtained from a variety of tissues and organs (Liu et al 2022 ) to be grafted into IVD matrix (Lv et al 2014 ) or, as previously described (Daly et al 2016 ; Chan et al 2014 ; Choi et al 2015 ; Tang et al 2012 ), MSCs with minor differences in potency and surface marker expression can be found endogenously in both AF and NP as a progenitor-like niche that is dormant with potential to support IVD repairment after stimulation. Although these endogenous cells can significantly uphold tissue balance, gradually replenishing the tissue during normal physiological conditions, the pathologic milieu of the host tissue is related to variations in their capacity for differentiation, cytokine secretion, or gene expression profile (Liu et al 2022 ; Chu et al 2022 ). Regarding exogenous MSCs, their source of origin also affects their profile.…”

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering

“…However, the NPCMs biodegraded over time, which resulted in the migration of ADSCs. ADSCs injected without NPCMs had no effects on NP regeneration according to the low DHI%, low water and ECM contents, and abnormal NP structure, and this is mainly because the suboptimal microenvironment of the degenerated IVD is harmful for the survival and function of transplanted ADSCs [3,59]. The NPCMs stimulate the NP-specific differentiation of ADSCs, which favor regeneration of the degenerated NP.…”

“…The bioscaffolds used in the IVD should be injectable to avoid injury to the IVD structure during transplantation. In addition, the transplanted bioscaffolds should have the ability to support cell survival, proliferation and differentiation and not aggravate the suboptimal microenvironment of the IVD [3,4]. However, ideal bioscaffolds that can meet these requirements are still lacking.…”

Stem cell homing in periodontal tissue regeneration

“…The possible mechanism might rely on the development of the scaffold system which is implanted into the damaged area (Lee et al, 2016;Abdulghani and Mitchell, 2019). The proper microenvironment created by the implanted scaffold will then promote the host stem cells to recruit and move through the vascular network or tissue interstitial space to the damaged tissue or organ, where the stem cells then proliferate, differentiate, and form tissue within the scaffold which eventually degrades, leaving only regenerated tissue (Zheng et al, 2019;Chu et al, 2022).…”