Current Stem Cell Research & Therapy - Volume 14, Issue 8, 2019

Low back pain is a prevalent socio-economic burden and is often associated with damaged or degenerated intervertebral discs (IVDs). When conservative therapy fails, removal of the IVD (discectomy), followed by intersomatic spinal fusion, is currently the standard practice in clinics. The remaining space is filled with an intersomatic device (cage) and with bone substitutes to achieve disc height compensation and bone fusion. As a complication, in up to 30% of cases, spinal non-fusions result in a painful pseudoarthrosis. Bone morphogenetic proteins (BMPs) have been clinically applied with varied outcomes. Several members of the BMP family, such as BMP2, BMP4, BMP6, BMP7, and BMP9, are known to induce osteogenesis. Questions remain on why hyper-physiological doses of BMPs do not show beneficial effects in certain patients. In this respect, BMP antagonists secreted by mesenchymal cells, which might interfere with or block the action of BMPs, have drawn research attention as possible targets for the enhancement of spinal fusion or the prevention of non-unions. Examples of these antagonists are noggin, gremlin1 and 2, chordin, follistatin, BMP3, and twisted gastrulation. In this review, we discuss current evidence of the osteogenic effects of several members of the BMP family on osteoblasts, IVD cells, and mesenchymal stromal cells. We consider in vitro and in vivo studies performed in human, mouse, rat, and rabbit related to BMP and BMP antagonists in the last two decades. We give insights into the effects that BMP have on the ossification of the spine. Furthermore, the benefits, pitfalls, and possible safety concerns using these cytokines for the improvement of spinal fusion are discussed.

Chronic pain is a common condition that seriously affects the quality of human life with variable etiology and complicated symptoms; people who suffer from chronic pain may experience anxiety, depression, insomnia, and other harmful emotions. Currently, chronic pain treatments are nonsteroidal anti-inflammatory drugs and opioids; these drugs are demonstrated to be insufficient and cause severe side effects. Therefore, research into new therapeutic strategies for chronic pain is a top priority. In recent years, stem cell transplantation has been demonstrated to be a potent alternative for the treatment of chronic pain. Mesenchymal stem cells (MSCs), a type of pluripotent stem cell, exhibit multi-directional differentiation, promotion of stem cell implantation, and immune regulation; they have also been shown to exert analgesic effects in several chronic pain models. Exosomes produced by MSCs have been demonstrated to relieve painful symptoms with fewer side effects. In this review, we summarize the therapeutic use of MSCs in various chronic pain studies. We also discuss ways to enhance the treatment effect of MSCs. We predict in the future, cell-free therapies for chronic pain will develop from exosomes secreted by MSCs.

Intervertebral disc (IVD) has a pivotal role in the maintenance of flexible motion. IVD degeneration is one of the primary causes of low back pain and disability, which seriously influences patients’ health, and increases the family and social economic burden. Recently, stem cell therapy has been proven to be more effective on IVD degeneration disease. However, stem cell senescence is the limiting factor in the IVD degeneration treatment. Senescent stem cells have a negative effect on the self-repair on IVD degeneration. In this review, we delineate that the factors such as telomerase shortening, DNA damage, oxidative stress, microenvironment and exosomes will induce stem cell aging. Recent studies tried to delay the aging of stem cells by regulating the expression of aging-related genes and proteins, changing the activity of telomerase, improving the survival microenvironment of stem cells and drug treatment. Understanding the mechanism of stem cell aging and exploring new approaches to delay or reverse stem cell aging asks for research on the repair of the degenerated disc.

Background: Breast cancer remains to be one of the deadliest forms of cancers, owing to the drug resistance and tumor relapse caused by breast cancer stem cells (BCSCs) despite notable advancements in radio-chemotherapies. Objectives: To find out novel therapeutics against breast cancer stem cells by aiming surface markers and signaling pathways. Methods: A systematic literature search was conducted through various electronic databases including, Pubmed, Scopus, Google scholar using the keywords "BCSCs, surface markers, signaling pathways and therapeutic options against breast cancer stem cell. Articles selected for the purpose of this review were reviewed and extensively analyzed. Results: Novel therapeutic strategies include targeting BCSCs surface markers and aberrantly activated signaling pathways or targeting their components, which play critical roles in self-renewal and defense, have been shown to be significantly effective against breast cancer. In this review, we represent a number of ways against BCSCs surface markers and hyper-activated signaling pathways to target this highly malicious entity of breast cancer more effectively in order to make a feasible and useful strategy for successful breast cancer treatment. In addition, we discuss some characteristics of BCSCs in disease progression and therapy resistance. Conclusion: BCSCs involved in cancer pathogenesis, therapy resistance and cancer recurrence. Thus, it is suggested that a multi-dimensional therapeutic approach by targeting surface markers and aberrantly activated signaling pathways of BCSCs alone or in combination with each other could really be worthwhile in the treatment of breast cancer.

Background: Multiple studies have focused on stem cell-based treatments for rotator cuff disorders; however, the outcomes are not consistent. Objectives: This systematic review and meta-analysis were performed to evaluate the effects of stem cells on rotator cuff healing. Methods: A detailed search of relevant studies was conducted in three databases including Pubmed/ Medline, Cochrane library, and Embase databases, using the following keywords: “rotator cuff” or “Tissue Engineering” AND “stem cell” from inception to January 01, 2019. The standard mean difference (SMD) and 95% confidence interval (CI) for each individual study were extracted from the original studies or calculated based on relevant data and pooled to obtain integrated estimates using random effects modeling. Results: A total of 22 studies were identified. The results demonstrated that the ultimate strain in the stem cell group was significantly higher than that in the control group at 4 and 8 weeks. Muscle weight in the stem cell group was higher than the control group at 8 weeks, while no significant differences were detected at 16 weeks. The stem cell group had lower visual analog scale scores (VAS) at 1, 3, and 6 months, and higher American shoulder and elbow surgeons score (ASES) at 3 months. In addition, the walking distance, time, and speed in the stem cell group were significantly superior to those in the control group. Conclusions: This meta-analysis confirms that stem cells improved the rehabilitation of rotator cuff disorders. However, larger-scale studies are needed to further support these findings.