Table 1.
Overview of reviews on preclinical studies about the application of MSCs for IVD regeneration published in the past five years. PubMed search with following query box: (((MSC) OR (mesenchymal stem cell)) OR (mesenchymal stromal cell)) AND ((intervertebral disc repair) OR (intervertebral disc regeneration)) Filters: Review, Systematic Review, in the last 5 years. Reviews with a focus on clinical trials were excluded. The search on PubMed was conducted on January 14, 2021.
| Study Design | Outcomes | References |
|---|---|---|
| Reviewing current uses and potential applications of MSCs in orthopedic surgery. | MSCs can be used for treating musculoskeletal diseases. Further research is needed to evaluate the safety and effectiveness of MSC treatment in orthopedics. | [50] |
| Reviewing current cell-based therapies for treating IDD, with an emphasis on endogenous repair strategies. | Intradiscal cell injections show promising results to reduce LBP. Endogenous repair with growth factors and chemokines has the potential to overcome hurdles of cell-based therapies. | [36] |
| Reviewing current knowledge about IDD and discussing recent advancements made with the GDF family for IVD regeneration. | GDF family members can stimulate anabolic processes when delivered to NP cells and promote NP-like differentiation when delivered to MSCs. | [51] |
| Reviewing characteristics and potency of progenitor cells in different IVD compartments. | IVD progenitor cells show a trilineage differentiation potential and express typical MSC markers. Aging and a degenerated microenvironment affect the fate of IVD progenitor cells. | [52] |
| Reviewing the successes, drawbacks, and the failures of stem cell-based regenerative medicine approaches to repair IDD. | MSC-based treatments for IDD are on the rise and many of them look promising. Nevertheless, it remains important to understand the fate and contribution of these cells and consequently to promote a safer outcome for stem cell-based approaches. | [53] |
| Researchers and clinicians discuss the pros and cons of MSC treatment for IVD regeneration. | Preclinical trials using MSCs for IVD regeneration look promising because of MSC proliferation characteristics, anabolic functionality and inflammation-modulatory properties. | [54] |
| Reviewing mechanisms of endogenous repair during IDD. | Endogenous stem/progenitor cell-based therapy is a promising approach for IDD. Biomimetic peptide biomaterials with signaling molecules can be designed to facilitate the survival and migration of IVD stem/progenitor cells. | [55] |
| Reviewing strategies for IVD repair using bioscaffolds and MSCs. | Preclinical studies with ovine and canine MSCs show impressive results for IVD repair. The authors also hypothesize that combined therapeutic approaches using biomaterial and cell-based therapies promise notable breakthroughs in IVD repair in the near future. | [56] |
| Reviewing the therapeutic potential of MSC-derived and IVD-derived extracellular vesicles for IDD. | MSC-derived extracellular vesicles promote ECM synthesis, IVD cell proliferation, and reduce inflammation and apoptosis. | [57] |
| Reviewing stem cell-based treatments, the molecular machinery and signaling pathways responsible for cartilage and IVD regeneration. | MSC-based therapies show a significant potential to revolutionize the treatment of cartilage defects and IDD. However, there are still many hurdles associated with isolating, expanding, differentiating, and preconditioning MSCs for transplantation into degenerated joints and IVDs. | [58] |
| Reviewing current stem cell therapies to treat discogenic LBP. | Preliminary animal models have shown the great potential of MSC implantation in order to restore the ECM and regenerate the IVD. | [59] |
| Reviewing different stem cell-based treatments for IDD. | The transplantation of adult stem cells has repeatedly shown to help regenerate the IVD’s ECM. However, the efficacy of adult stem cell transplantation for IDD treatment is still unclear and therefore needs further investigation. | [60] |
| Reviewing different stem cell types used as a cell-based therapy for IVD regeneration. | Adult stem cell therapy shows promise for the treatment of IDD. Recent studies have demonstrated the effectiveness of autologous MSC transplantation for IVD regeneration in reproducible animal models. | [61] |
| Reviewing characteristics of healthy and degenerated IVD microenvironments and their influence on IVD and MSC biological activity and viability. | IDD causes an aggravation of the hostile microenvironment for tissue repair and cell survival in the IVD. However, intradiscal cell therapy with MSCs has the potential to regenerate the IVD and to reverse the changes of IDD. | [41] |
| Reviewing the latest advances in repairing degenerated IVDs using MSCs, pluripotent stem cells, and NP progenitor cells. | Various animal models have shown that intradiscally transplanted MSCs generally fail to survive and engraft into the IVD niche, whereas pluripotent stem cells and NP progenitor cells can survive successfully. | [62] |
Abbreviations: IVD: intervertebral disc, MSC: mesenchymal stromal cell, IDD: intervertebral disc degeneration, LBP: low back pain, GDF: growth and differentiation factor, NP: nucleus pulposus, AF: annulus fibrosus, PAX: paired box, SHH: sonic hedgehog signaling molecule, SOX: SRY-Box transcription factor, FOXA: forkhead box, and ECM: extracellular matrix.