Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives

Regmi, Shobha; Pathak, Shiva; Kim, Jong Oh; Yong, Chul Soon; Jeong, Jee–Heon

doi:10.1016/j.ejcb.2019.04.002

Cited by 225 publications

(159 citation statements)

References 291 publications

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“…In past decades, MSCs have been widely used to treat inflammatory diseases 63 . While many clinical studies have reported that the efficacy of MSCs infusion are supposed to be improved.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

Xie

Zeng³

et al. 2020

Cell Death Dis

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Ankylosing spondylitis (AS) is a chronic inflammatory disease possessing a morbid serum microenvironment with enhanced oxidative stress. Long-term exposure to an oxidative environment usually results in cellular senescence alone with cellular dysfunction. Mesenchymal stem cells (MSCs) are a kind of stem cell possessing strong capabilities for immunoregulation, and senescent MSCs may increase inflammation and participate in AS pathogenesis. The objective of this study was to explore whether and how the oxidative serum environment of AS induces MSC senescence. Here, we found that AS serum facilitated senescence of MSCs in vitro, and articular tissues from AS patients exhibited higher expression levels of the cell cycle arrest-related proteins p53, p21 and p16. Importantly, the levels of advanced oxidative protein products (AOPPs), markers of oxidative stress, were increased in AS serum and positively correlated with the extent of MSC senescence induced by AS serum. Furthermore, MSCs cultured with AS serum showed decreased mitochondrial membrane potential and ATP production together with a reduced oxygen consumption rate. Finally, we discovered that AS serum-induced mitochondrial dysfunction resulted in elevated reactive oxygen species (ROS) in MSCs, and ROS inhibition successfully rescued MSCs from senescence. In conclusion, our data demonstrated that the oxidative serum environment of AS facilitated MSC senescence through inducing mitochondrial dysfunction and excessive ROS production. These results may help elucidate the pathogenesis of AS and provide potential targets for AS treatment.

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“…In past decades, MSCs have been widely used to treat inflammatory diseases 63 . While many clinical studies have reported that the efficacy of MSCs infusion are supposed to be improved.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

Xie

Zeng³

et al. 2020

Cell Death Dis

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“…MSC-based cell therapies focus on the improvement of osteoinduction through supplementation of tissue engineered construct (TEC) with isolated mesenchymal stem cells cultured in osteogenic medium [93]. The success of all clinical studies using MSCs and ASCs in bone regeneration depends on cell viability, cell homing capacity and engraftment into injured tissue [94]. Allogenic mesenchymal stem cells have been noted to achieve therapeutic effects in in vivo mouse studies investigating non-union bone [14].…”

Section: Msc-and Asc-based Cell Therapiesmentioning

confidence: 99%

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

Hutchings

Moncrieff

Dompe

et al. 2020

JCM

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The deterioration of the human skeleton’s capacity for self-renewal occurs naturally with age. Osteoporosis affects millions worldwide, with current treatments including pharmaceutical agents that target bone formation and/or resorption. Nevertheless, these clinical approaches often result in long-term side effects, with better alternatives being constantly researched. Mesenchymal stem cells (MSCs) derived from bone marrow and adipose tissue are known to hold therapeutic value for the treatment of a variety of bone diseases. The following review summarizes the latest studies and clinical trials related to the use of MSCs, both individually and combined with other methods, in the treatment of a variety of conditions related to skeletal health. For example, some of the most recent works noted the advantage of bone grafts based on biomimetic scaffolds combined with MSC and growth factor delivery, with a greatly increased regeneration rate and minimized side effects for patients. This review also highlights the continuing research into the mechanisms underlying bone homeostasis, including the key transcription factors and signalling pathways responsible for regulating the differentiation of osteoblast lineage. Paracrine factors and specific miRNAs are also believed to play a part in MSC differentiation. Furthering the understanding of the specific mechanisms of cellular signalling in skeletal remodelling is key to incorporating new and effective treatment methods for bone disease.

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“…Attributed to their advantages, mesenchymal stem cells (MSCs) stand out from multiple stem cells and become the most promising choice for both autologous and allogeneic transplantation (Maxson et al, 2012;Wei et al, 2013;Poltavtseva et al, 2018). However, the application of MSCs from bench to bedside encounters many challenges, such as low cell dose, low survival rate and poor potency (Silva et al, 2018;Regmi et al, 2019). Considerable efforts have been made to improve the regenerative efficiency of MSCs in vivo.…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

Xia

et al. 2020

PeerJ

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Background Different phenotypes of macrophages (M0, M1 and M2 Mφs) have been demonstrated to play distinct roles in regulating mesenchymal stem cells in various in vitro and in vivo systems. Our previous study also found that cell-conditioned medium (CM) derived from M1 Mφs supported the proliferation and adipogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs), whereas CM derived from either M0 or M2 Mφs showed an enhanced effect on cell osteogenic differentiation. However, the underlying mechanism remains incompletely elucidated. Exosomes, as key components of Mφ-derived CM, have received increasing attention. Therefore, it is possible that exosomes may modulate the effect of Mφ-derived CM on the property of BMMSCs. This hypothesis was tested in the present study. Methods In this study, RAW264.7 cells were induced toward M1 or M2 polarization with different cytokines, and exosomes were isolated from the unpolarized (M0) and polarized (M1 and M2) Mφs. Mouse BMMSCs were then cultured with normal complete medium or inductive medium supplemented with M0-Exos, M1-Exos or M2-Exos. Finally, the proliferation ability and the osteogenic, adipogenic and chondrogenic differentiation capacity of the BMMSCs were measured and analyzed. Results We found that only the medium containing M1-Exos, rather than M0-Exos or M2-Exos, supported cell proliferation and osteogenic and adipogenic differentiation. This was inconsistent with CM-based incubation. In addition, all three types of exosomes had a suppressive effect on chondrogenic differentiation. Conclusion Although our data demonstrated that exosomes and CM derived from the same phenotype of Mφs didn’t exert exactly the same cellular influences on the cocultured stem cells, it still confirmed the hypothesis that exosomes are key regulators during the modulation effect of Mφ-derived CM on BMMSC property.

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Mesenchymal stem cell therapy for the treatment of inflammatory diseases: Challenges, opportunities, and future perspectives

Cited by 225 publications

References 291 publications

Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

Oxidative stress-mediated mitochondrial dysfunction facilitates mesenchymal stem cell senescence in ankylosing spondylitis

Bone Regeneration, Reconstruction and Use of Osteogenic Cells; from Basic Knowledge, Animal Models to Clinical Trials

Exosomes derived from M0, M1 and M2 macrophages exert distinct influences on the proliferation and differentiation of mesenchymal stem cells

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