**6. MSCs in femoral head necrosis**

Avascular necrosis of the femoral head (ANFH) is a serious clinical problem. If untreated, about 80% of ANFH progresses to the collapse of the head within 1–4 years [48]. Numerous clinical methods have been tried, including core decompression (CD), a commonly used method for treating the early stages of ANFH. The presumption is that CD can reduce the intraosseous pressure and also stimulate stem cell regeneration. But the outcome of CD is variable and is still controversial.

With the development of non-biological materials, MSCs and tissue engineering techniques, the treatment of ANFH has been significantly improved recently [49]. For example, it was reported that the efficacy of MSCs transplantation group was significantly better than that of the pure medullary decompression group [50]. In another study, 100 patients with early-stage ANFH were recruited and randomly assigned to BMMSC treatment or CD treatment only [51], a similar result was observed, that is, this intervention was proved to be safe and more effective in delaying or avoiding FH collapse. In another study of eight patients with bilateral femoral head necrosis, the researchers performed the medullary decompression on one side, while on the other side medullary decompression MSCs transplantation. The Harris hip score (HHS) and VAS score of the MSCs transplantation group were significantly improved, and the results of MRI quantitative analysis showed a significant decrease in necrosis area [52]. Consistently, another study found that the group of MSCs had a significantly superior recovery of the early stages of necrosis [53].

by promoting expression of hypoxia-inducible factor to repair and reconstruct degenerated

Clinical Applications of Mesenchymal Stromal Cells (MSCs) in Orthopedic Diseases

http://dx.doi.org/10.5772/intechopen.76868

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In a recent study, under fluoroscopic guidance, the BMCs were injected into the nucleus pulposus of 26 patients' with chronic (>6 months) discogenic low back pain [61]. These authors found the evidence of safety and feasibility in the non-surgical treatment of discogenic pain using autologous BMCs with durable pain relief (71% VAS reduction) and Oswestry Disability

Overall, the BMSCs as a treatment of degenerated intervertebral disc is successful both in an animal model and in clinical studies; however, there are no long-term follow-up results and the number of reports and the number of cases are still relatively low. Another concern is that, at least in theory, BMSCs may cause osteophyte formation in the vertebral isthmus when it is released from the nucleus. Further clinical trials are needed to clarify these

Osteoporosis is a common metabolic bone disease, characterized by loss of bone mass, bone density reduction, and bone structure damage, which leads to increased bone fragility and risks of bone fracture [62]. The exact underlying mechanisms of osteoporosis are still unclear, but a shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts partly contributes to osteoporosis [63]. Furthermore, it was observed that osteoclast activity (bone resorption) was enhanced, while osteoblast function (bone formation) decreased. For this reason, the drugs that inhibit the activity of osteoclasts have been widely used in clinical practice; however, these drugs have many complications, such as mandibular necrosis, reflux esophagitis, and atypical fracture [62, 64]. Recently, it is found that the decrease of BMSC to osteogenic differentiation and the increase of lipid differentiation is an important factor in the pathogenesis of osteoporosis [65, 66], therefore, one of the new ways to inhibit osteoporosis is to promote osteogenesis differentiation of endogenous BMSCs. In the meantime, BMSCs transplantation can also effectively increase bone mass and density, increase bone mechanical strength, correct the imbalance in bone metabolism, and increase bone formation, and is expected to provide a new strategy and method for the treatment of

Scholars have carried out a large number of studies, including signal transduction, gene transcription, and post-transcriptional level, and found that miRNA and epigenetic modifications are probably the main mechanisms for BMSC differentiation [63]. In addition, conserved signal regulation, mechanical stimuli, radiation, and diet also play important roles in regulating the differentiation fate of MSCs. Even though an MSC transplant could, at least in theory, provide a treatment for osteoporosis, the clinical trials of MSCs in osteoporosis have just begun; nevertheless, the animal studies have already found that autograft or allogeneic MSC transplantation can increase the bone mass of animal models of osteoporosis [66, 67]. Since

intervertebral disc [60].

concerns.

osteoporosis [67].

**8. MSCs in osteoporosis**

Index improvements (>64%) through 2 years.

However, there have been reports of unsatisfactory success rates for end-stage osteonecrosis of the femoral head (ONFH), even with MSCs [54]. To improve the outcome, Zhao et al. describe a modified technique using BMSCs associated with porous tantalum rod implantation combined with vascularized iliac grafting for the treatment of end-stage ONFH, and they followed up for 5 years, and these authors found that Harris hip score was improved from 38.74 ± 5.88 points (range 22–50) to 77.23 ± 14.75 points (range 33–95) [55]. It is worthy to mention that, in this procedure, approximately 10 mL of bone marrow from the subtrochanteric region was directly aspirated once the decompression tunnel was established during the surgery, avoiding the need for bone marrow aspiration from the iliac crest.
