A Brief Overview of Global Trends in MSC-Based Cell Therapy

Jovic, Dragomirka; Yu, Yingjia; Wang, Dan; Wang, Kuixing; Li, Hanbo; Xu, Fengping; Liu, Chenglong; Liu, Junnian; Luo, Yonglun

doi:10.1007/s12015-022-10369-1

Cited by 115 publications

(73 citation statements)

References 194 publications

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“…Hospital Essen, University of Duisburg-Essen, Essen, Germany. 3 National University of Ireland Galway, Galway, Ireland. 4 LUMC, Sequencing Analysis Support Core, Leiden, The Netherlands.…”

Section: Supplementary Informationmentioning

confidence: 99%

“…The lack of effective treatments for inflammatory diseases as well as major age-related diseases, e.g., chronic Inflammatory Bowel Disease, neurodegenerative disease and osteoarthritis, imposes a huge economic burden on individual patients and health care systems [1,2]. In that respect, caretakers have high hopes for the application of cell therapy in the clinic using human adult mesenchymal stromal cells (hMSCs) [3]. Upon exposure to signals associated with the in vivo injured environment hMSCs are known to respond with a process named licensing.…”

Section: Introductionmentioning

confidence: 99%

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Characterizing the secretome of licensed hiPSC-derived MSCs

et al. 2022

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Although mesenchymal stromal cells (MSCs) from primary tissues have been successfully applied in the clinic, their expansion capabilities are limited and results are variable. MSCs derived from human-induced pluripotent stem cells (hiMSCs) are expected to overcome these limitations and serve as a reproducible and sustainable cell source. We have explored characteristics and therapeutic potential of hiMSCs in comparison to hBMSCs. RNA sequencing confirmed high resemblance, with average Pearson correlation of 0.88 and Jaccard similarity index of 0.99, and similar to hBMSCs the hiMSCs released extracellular vesicles with in vitro immunomodulatory properties. Potency assay with TNFα and IFNγ demonstrated an increase in well-known immunomodulatory genes such as IDO1, CXCL8/IL8, and HLA-DRA which was also highlighted by enhanced secretion in the media. Notably, expression of 125 genes increased more than 1000-fold. These genes were predicted to be regulated by NFΚB signaling, known to play a central role in immune response. Altogether, our data qualify hiMSCs as a promising source for cell therapy and/or cell-based therapeutic products. Additionally, the herewith generated database will add to our understanding of the mode of action of regenerative cell-based therapies and could be used to identify relevant potency markers.

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“…Hospital Essen, University of Duisburg-Essen, Essen, Germany. 3 National University of Ireland Galway, Galway, Ireland. 4 LUMC, Sequencing Analysis Support Core, Leiden, The Netherlands.…”

Section: Supplementary Informationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterizing the secretome of licensed hiPSC-derived MSCs

et al. 2022

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“…How MSCs fit into the landscape of regenerative medicine: The connection to very small embryonic-like stem cells Unlike hES and iPS cells, MSCs have entered the clinics, and have shown abundant promise (Jovic et al, 2022). As we recently discussed (Bhartiya et al, 2022a), the beneficial effects of transplanting MSCs, as reported in multiple clinical trials (Squillaro et al, 2016;Esfandyari et al, 2020), come from their capacity to rejuvenate (i.e., improve the microenvironment/niche of) diseased tissues by providing paracrine support to the tissue-resident, endogenous very small embryonic-like stem cells (VSELs), which in turn regenerate the diseased tissues.…”

Section: Introductionmentioning

confidence: 99%

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front “war” against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and “reprogram” into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the “light at the end of the tunnel.”

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“…Moreover, despite enhanced tissue repair and functioning after MSCs therapy, the studies have not found significant evidence for the differentiation of MSCs into other cell types. Therefore, the prevailing view now is that MSCs perform their therapeutic actions via paracrine mechanisms rather than by direct differentiation and cell replacement (20,21). One of the paracrine effects of MSCs is modulation of the immune system.…”

Section: Introductionmentioning

confidence: 99%

Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

Sarsenova

Kim²,

Raziyeva³

et al. 2022

Front. Immunol.

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Considering the unique therapeutic potential of mesenchymal stem cells (MSCs), including their immunosuppressive and immunomodulatory properties as well as their ability to improve tissue regeneration, these cells have attracted the attention of scientists and clinicians for the treatment of different inflammatory and immune system mediated disorders. However, various clinical trials using MSCs for the therapeutic purpose are conflicting and differ from the results of promising preclinical studies. This inconsistency is caused by several factors such as poor migration and homing capacities, low survival rate, low level of proliferation and differentiation, and donor-dependent variation of the cells. Enhancement and retention of persistent therapeutic effects of the cells remain a challenge to overcome in MSC-based therapy. In this review, we summarized various approaches to enhance the clinical outcomes of MSC-based therapy as well as revised current and future perspectives for the creation of cellular products with improved potential for diverse clinical applications.

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A Brief Overview of Global Trends in MSC-Based Cell Therapy

Cited by 115 publications

References 194 publications

Characterizing the secretome of licensed hiPSC-derived MSCs

Characterizing the secretome of licensed hiPSC-derived MSCs

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells

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