Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial

Skrahin, Aliaksandr; Ahmed, Raija; Ferrara, Giovanni; Rane, Lalit; Poiret, Thomas; Isaikina, Yanina; Skrahina, Alena; Zumla, Alimuddin; Maeurer, Markus

doi:10.1016/s2213-2600(13)70234-0

Cited by 124 publications

(106 citation statements)

References 81 publications

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“…136 Mesenchymal stromal cells (MSC) are nonhematopoietic progenitor cells with immunomodulatory and antibacterial properties, [137][138] that improve immune responses and lung pathology in human and murine TB. [139][140] Another immunotherapeutic approach involves modulation of immune regulatory cells, specifically myeloid-derived suppressor cells (MDSC) [141][142] MDSC are increased in TB, display T-cell immunosuppressive properties, [143][144][145] and harbour Mtb, suggesting that MDSC-targeting strategies should also be considered in TB HDT design. The promise of use T-cell therapy, with or without T-cell receptor (TCR) manipulations to increase affinity for antigen has shown promise for CMV treatment, and could be beneficial in TB.…”

Section: Cellular Therapymentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

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313

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Cellular Therapymentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

Self Cite

313

275

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“…MSCs also showed great results when transplanted with T cells, controlling inflammatory activity in order to create the proper microenvironment for cell transplantation [24] . The immunomodulating effect of MSCs has also been reported in other clinical trials and MSCs have been shown to play an important role as immunomodulators and angiogenic agents in drug resistant patients as well as in patients with cerebral palsy, critical limb ischemia and kidney transplants [25][26][27][28][29][30][31][32] . In another study conducted with 40 patients, bone regeneration was achieved when a great number of CD34 + cells were transplanted to the lesion site, 20 patients achieved mature bone regeneration, even in the group that received a low number of cells 4 patients achieved bone regeneration.…”

Section: Mesenchymal Stem Cells/bone Marrow Stem Cellsmentioning

confidence: 78%

Adult stem cells in neural repair: Current options, limitations and perspectives

Mariano¹

2015

WJSC

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Stem cells represent a promising step for the future of regenerative medicine. As they are able to differentiate into any cell type, tissue or organ, these cells are great candidates for treatments against the worst diseases that defy doctors and researchers around the world. Stem cells can be divided into three main groups: (1) embryonic stem cells; (2) fetal stem cells; and (3) adult stem cells. In terms of their capacity for proliferation, stem cells are also classified as totipotent, pluripotent or multipotent. Adult stem cells, also known as somatic cells, are found in various regions of the adult organism, such as bone marrow, skin, eyes, viscera and brain. They can differentiate into unipotent cells of the residing tissue, generally for the purpose of repair. These cells represent an excellent choice in regenerative medicine, every patient can be a donor of adult stem cells to provide a more customized and efficient therapy against various diseases, in other words, they allow the opportunity of autologous transplantation. But in order to start clinical trials and achieve great results, we need to understand how these cells interact with the host tissue, how they can manipulate or be manipulated by the microenvironment where they will be transplanted and for how long they can maintain their multipotent state to provide a full regeneration.

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“…Recently, Skrahin et al [16] demonstrated Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial. MSCs as an adjunct therapy are safe and can be further explored for the treatment of patients with MDR or XDR tuberculosis in combination with standard drug regimens.…”

Section: Mesenchymal Stromal Cells (Mscs)mentioning

confidence: 99%

Stem Cell Therapy: an Adjunct in the Treatment of MDR Tuberculosis

Khan

Zaidi

Thawani

2017

JSRT

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Tuberculosis is a global health issue and a major cause of death worldwide. Emerging infectious disease as multidrug resistance and extensively drug resistance tuberculosis triggers the importance to improve the current therapy or else develop an innovative approach. Currently stem cell transplantation emerged as new therapeutic to overcome tuberculosis. Recent studies provide an opportunity to explore stem cell in treatment of drug resistant tuberculosis. This review is in concern with the regime, future effect and challenges of stem cell therapy in drug resistant patients. Keywords:

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Autologous mesenchymal stromal cell infusion as adjunct treatment in patients with multidrug and extensively drug-resistant tuberculosis: an open-label phase 1 safety trial

Cited by 124 publications

References 81 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Adult stem cells in neural repair: Current options, limitations and perspectives

Stem Cell Therapy: an Adjunct in the Treatment of MDR Tuberculosis

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