Author details

time [106, 109–111]. MTB infects and persists in a dormant form inside BM-MSCs even after successful antimicrobial therapy [112]. Virulent mycobacteria can manipulate Toll-like receptors and certain signaling pathways including nuclear factor kappa-light-chain-enhancer of activated B cells in order to survive inside the BM stem cells [112]. MSCs can increase NO production in Mycobacterium abscessusinfected macrophages through activation of tumor necrosis factor (TNF)-α in the presence of IFN-γ [113]. The cellular crosstalk between TNF-α and prostaglandin-E2 is essential for the increased production of NO in macrophages [113]. Consequently, MSCs may become an ideal choice as adjunct therapy in MDR and XDR TB particularly in individuals with comorbid medical conditions [102, 103, 114]. There are three main clinical trials on the use of MSCs in the treatment of MDR/XDR TB [115–117]. In the first trial, 27 patients with MDR/XDR TB who had been unsuccessfully treated with conventional anti-TB chemotherapy received autologous MSCs, the following results were obtained: all patients showed positive responses to MSC therapy, bacterial discharge from lungs was abolished in 20 patients, tissue damage and lung cavitation resolved in 11 patients, and persistent remission of TB was encountered in 56% of patients after 2 years of autologous MSC transplantation [115]. In the second study, a phase I clinical trial, 36 patients with MDR/XDR TB received anti-TB chemotherapy for 4 weeks; then, they were subjected to autologous MSC transplantation [116]. Six months after autologous transplantation of MSCs: no major adverse events were reported, 70% of patients showed radiological improvement, while 16.7% of patients showed stable radiological appearances. Eighteen months after autologous transplantation of MSCs: 53% of patients were cured, while 10% of patients showed evidence of treatment failure [116]. In the third study, a randomized clinical trial, 72 patients with MDR/XDR TB were included: 36 patients (control group) received conventional anti-TB chemotherapy only, and the other 36 patients (study group) received anti-TB chemotherapy and autologous MSC transplantation [117]. Successful outcomes were encountered in 81% of the study group and 40% of the control group. So, the addition of autologous MSC transplantation to conventional anti-TB chemotherapy significantly enhanced the response rates in patients with MDR/XDR TB [117]. Therefore, combining standard anti-TB chemotherapy with autologous MSC transplantation may ultimately become valuable in increasing the efficacy of anti-TB treatment in patients

Update on Mesenchymal and Induced Pluripotent Stem Cells

Administration of human MSCs does not have negative impact on host response against Aspergillus fumigatus [118, 119]. Also, Aspergillus fumigatus does not stimulate MSCs to secrete cytokines that play a major role in the pathogenesis of GVHD indicating that Aspergillus fumigatus is not involved in the pathogenesis of GVHD following HSCT. In an animal model, infusion of BM-MSCs into mice infected with

Since their first description in the 1960s, the history of MSCs has witnessed steady progress that ultimately resulted in their clinical application in the treatment of many disorders including several infectious diseases. Although the success has not been uniform with regard to various infections and despite the gap between the achievements in animal studies and results of clinical trials in humans, plenty of

Paracoccidioides brasiliensis failed to induce any antimicrobial effects.

with MDR-TB [2, 102, 115, 116].

9. MSCs in fungal infections

10. Conclusions and future directions

38

Khalid Ahmed Al-Anazi<sup>1</sup> \*, Waleed K. Al-Anazi<sup>2</sup> and Asma M. Al-Jasser<sup>3</sup>

1 Department of Hematology and Hematopoietic Stem Cell Transplantation, Oncology Center, King Fahad Specialist Hospital, Dammam, Saudi Arabia

2 Section of Cytogenetics, Department of Pathology, King Fahad Specialist Hospital, Dammam, Saudi Arabia

3 Department of Research and Studies, General Directorate of Health Affairs in Riyadh Region, Ministry of Health, Riyadh, Saudi Arabia

\*Address all correspondence to: kaa\_alanazi@yahoo.com

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
