Therapeutic Applications of Genes and Gene-Engineered Mesenchymal Stem Cells for Femoral Head Necrosis

Abstract

Osteonecrosis of the femoral head (ONFH) is a common and disabling joint disease. Although there is no clear consensus on the complex pathogenic mechanism of ONFH, trauma, abuse of glucocorticoids, and alcoholism are implicated in its etiology. The therapeutic strategies are still limited, and the clinical outcomes are not satisfactory. Mesenchymal stem cells (MSCs) have been shown to exert a positive impact on ONFH in preclinical experiments and clinical trials. The beneficial properties of MSCs are due, at least in part, to their ability to home to the injured tissue, secretion of paracrine signaling molecules, and multipotentiality. Nevertheless, the regenerative capacity of transplanted cells is impaired by the hostile environment of necrotic tissue in vivo, limiting their clinical efficacy. Recently, genetic engineering has been introduced as an attractive strategy to improve the regenerative properties of MSCs in the treatment of early-stage ONFH. This review summarizes the function of several genes used in the engineering of MSCs for the treatment of ONFH. Further, current challenges and future perspectives of genetic manipulation of MSCs are discussed. The notion of genetically engineered MSCs functioning as a ''factory'' that can produce a significant amount of multipotent and patient-specific therapeutic product is emphasized.

microRNA‐148a‐3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head

“…2 At present, the treatment and clinical results are not perfect in ONFH. 3 Notably, there is the decrease of the proliferation and osteogenesis as well as the increase of apoptosis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs) from patients with ONFH. 4 Therefore, this study attempts to research a new therapeutic method for ONFH based on BMSCs.…”

Characterization of wild-type and STAT3 signaling-suppressed mesenchymal stem cells obtained from hemovac blood concentrates

“…STAT3 is a transcription factor belonging to the STAT protein family (41,42) that is activated by inflammatory cytokines, including in diseases associated with chronic inflammation and fibrosis (42)(43)(44)(45)(46)(47). The restoration of stem cell function by STAT3 signaling inhibition has been previously evaluated (48)(49)(50)(51). For instance, STAT3 signaling inhibition in MSCs from the adipose tissue resulted in improved antiinflammatory response and reduced inflammation (50).…”

“…Therefore, our data support the future clinical applications of iSTAT3-MSCs. If iSTAT3-MSCs, generated after TKA surgery are stored in a freezer, they can be used to resolve bone disorders, including fractures, non-union fractures, and avascular necrosis (51,(54)(55)(56). Furthermore, since after TKA, patients mainly use the non-operated leg, which can lead to injury in the articular cartilage of the knee joint, iSTAT3-MSCs, with enhanced chondrogenic potential, can be used to treat potential cartilage defects of non-operated knees.…”

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head

“…They can also be derived from adipose tissue or umbilical cord (Andriolo et al, 2018) and can be injected intra-arterially or directly into the necrotic area. MSCs have been shown to repair and regenerate bone due to their multipotentiality, paracrine signaling molecules, and "ability to home to the injured tissue" [89]. The advantage of cellular therapies are that they are potentially less invasive than surgical treatment [90].…”