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Human MSC Therapy – An Efficient Alternative Treatment for Mycobacterial Infections?

Review of “Donor‐defined mesenchymal stem cell antimicrobial potency against nontuberculous mycobacterium” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Recent research from the laboratory of Tracey L. Bonfield (Case Western Reserve University, Cleveland, OH, USA) underscored the antimicrobial, anti‐inflammatory, and antifibrotic potential of human mesenchymal stem cells (MSCs) [1-3] and their exciting ability to improve the effectiveness of antibiotics [4]. In their new STEM CELLS Translational Medicine article, researchers from the Bonfield lab now report on the potential of human MSCs to treat non-tuberculous mycobacterial infections (a difficult to treat and significantly impair the quality of life and survival of patients [5]) using a previously reported protocol that monitors mycobacterial growth, metabolism, and survival over the course of a week [6]. Bonfield et al. now report that human MSC administration may represent a safe and efficient alternative therapeutic strategy for chronic infections of hard-to-treat bacteria [7].

Initial in vitro studies demonstrated that human MSCs and the MSC secretome (to a lesser degree) possessed anti-mycobacterial potency and the ability to enhance the sensitivity of mycobacteria to antibiotic treatment; however, the study highlighted significant variability in the potency of human MSCs in the treatment of M. intracellulare and M. avium individually or a combined infection. Encouragingly, subsequent in vivo analyses in mice suffering from a sustained non-tuberculous mycobacterial infection in the lungs using a standardized agarose bead model revealed that human MSC treatment could attenuate various pathogenic phenotypes (See Figure).

Interestingly, the authors noted that different batches of human MSCs displayed differing anti-mycobacterial activity and, therefore, they sought to uncover potential biological response mediators linked to improved therapeutic outcomes. Their subsequent analysis suggested that the ability of human MSCs to produce heme oxygenase 1 (HMOX‐1), interleukin (IL)‐6 (which both redirect host immunity), and macrophage inflammatory protein 3α (CCL20) (an antibacterial mediator) function as potential biomarkers for the capacity of human MSCs to reduce non-tuberculous mycobacterial infections.

The authors anticipate that these findings will pave the way towards the development of human MSC therapy as a safe and effective alternative to the treatment of non-tuberculous mycobacterial infections with antibiotic macrolides, which are both toxic and often inefficient [8].

For more on the development of human mesenchymal stem cell therapy as an effective means to treat non-tuberculous mycobacterial infections, stay tuned to the Stem Cells Portal!

References

  1. Sutton MT, Fletcher D, Episalla N, et al., Mesenchymal Stem Cell Soluble Mediators and Cystic Fibrosis. Journal of Stem Cell Research & Therapy 2017;7.
  2. Goldstein BD, Lauer ME, Caplan AI, et al., Chronic asthma and Mesenchymal stem cells: Hyaluronan and airway remodeling. Journal of Inflammation 2017;14:18.
  3. Sutton MT, Fletcher D, Ghosh SK, et al., Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment. Stem Cells International 2016;2016:5303048.
  4. Bonfield TL, Lennon DP, Ghosh SK, et al., Cell based therapy aides in infection and inflammation resolution in the murine model of cystic fibrosis lung disease. Stem Cell Discovery 2013;3:139-153.
  5. Drummond WK and Kasperbauer SH, Nontuberculous Mycobacteria: Epidemiology and the Impact on Pulmonary and Cardiac Disease. Thoracic Surgery Clinics 2019;29:59-64.
  6. Auster L, Sutton M, Gwin MC, et al., Optimization of In Vitro Mycobacterium avium and Mycobacterium intracellulare Growth Assays for Therapeutic Development. Microorganisms 2019;7.
  7. Bonfield TL, Sutton MT, Fletcher DR, et al., Donor-defined mesenchymal stem cell antimicrobial potency against nontuberculous mycobacterium. STEM CELLS Translational Medicine 2021;10:1202-1216.
  8. Lakoš AK, Pangerčić A, Gašparić M, et al., Safety and effectiveness of azithromycin in the treatment of respiratory infections in children. Current Medical Research and Opinion 2012;28:155-162.