Isolation and characterization of mesenchymal stem cells in orthopaedics and the emergence of compact bone mesenchymal stem cells as a promising surgical adjunct

The potential clinical and economic impact of mesenchymal stem cell(MSC)therapy is immense.MSCs act through multiple pathways:(1)as“trophic”cells,secreting various factors that are immunomodulatory,anti-inflammatory,antiapoptotic,proangiogenic,proliferative,and chemoattractive;(2)in conjunction with cells native to the tissue they reside in to enhance differentiation of surrounding cells to facilitate tissue regrowth.Researchers have developed methods for the extraction and expansion of MSCs from animal and human tissues.While many sources of MSCs exist,including adipose tissue and iliac crest bone graft,compact bone(CB)MSCs have shown great potential for use in orthopaedic surgery.CB MSCs exert powerful immunomodulatory effects in addition to demonstrating excellent regenerative capacity for use in filling boney defects.CB MSCs have been shown to have enhanced response to hypoxic conditions when compared with other forms of MSCs.More work is needed to continue to characterize the potential applications for CB MSCs in orthopaedic trauma.

IDO1 in cancer: a Gemini of immune checkpoints

Indoleamine 2,3-dioxygenase 1(IDO1)is a rate-limiting metabolic enzyme that converts the essential amino acid tryptophan(Trp)into downstream catabolites known as kynurenines.Coincidently,numerous studies have demonstrated that IDO1 is highly expressed in multiple types of human cancer.Preclinical studies have further introduced an interesting paradox:while single-agent treatment with IDO1 enzyme inhibitor has a negligible effect on decreasing the established cancer burden,approaches combining select therapies with IDO1 blockade tend to yield a synergistic benefit against tumor growth and/or animal subject survival.Given the high expression of IDO1 among multiple cancer types along with the lack of monotherapeutic efficacy,these data suggest that there is a more complex mechanism of action than previously appreciated.Similar to the dual faces of the astrological Gemini,we highlight the multiple roles of IDO1 and review its canonical association with IDO1-dependent tryptophan metabolism,as well as documented evidence confirming the dispensability of enzyme activity for its immunosuppressive effects.The gene transcript levels for IDO1 highlight its strong association with T-cell infiltration,but the lack of a universal prognostic significance among all cancer subtypes.Finally,ongoing clinical trials are discussed with consideration of IDO1-targeting strategies that enhance the efficacy of immunotherapy for cancer patients。