Myths, reality and future of mesenchymal stem cell therapy

Полтавцева, Р. А.; Poltavtsev, A. V.; Луценко, Г. В.; Svirshchevskaya, E. V.

doi:10.1007/s00441-018-2961-4

Cited by 23 publications

(22 citation statements)

References 99 publications

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“…During the past several decades, stem cell therapy has been the focus of tissue engineering and regenerative medicine (Wei et al, 2013;Thurairajah, Broadhead & Balogh, 2017). 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).…”

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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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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“…Difficult to produce enough yield to be effective in humans [6] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [6,54] Systemic administration has not reflected targeting potential [6] Difficult to produce enough yield to be effective in humans [10,64] All isolation techniques have cons, including time, monetary cost, forming aggregates, introducing contaminants [16,63,66] No single way to manufacture exosomes of a specific potency [10,16] advances over the past several years, challenges such as batch consistency and purity remain when transitioning from rodent models of lung disease to large-scale clinical trials [41]. Nevertheless, MSC-exosomes offer an alternative to cellular therapies that may provide similar regenerative abilities, devoid of adverse effects following cellular administration.…”

Section: Consmentioning

confidence: 99%

Exosome therapeutics for lung regenerative medicine

Popowski

Lutz

et al. 2020

J of Extracellular Vesicle

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Exosomes are 30 to 100 nm extracellular vesicles that are secreted by many cell types. Initially viewed as cellular garbage with no biological functions, exosomes are now recognized for their therapeutic potential and used in regenerative medicine. Cell-derived exosomes are released into almost all biological fluids, making them abundant and accessible vesicles for a variety of diseases. These naturally occurring nanoparticles have a wide range of applications including drug delivery and regenerative medicine. Exosomes sourced from a specific tissue have been proven to provide greater therapeutic effects to their native tissue, expanding exosome sources beyond traditional cell lines such as mesenchymal stem cells. However, standardizing production and passing regulations remain obstacles, due to variations in methods and quantification techniques across studies. Additionally, obtaining pure exosomes at sufficient quantities remains difficult due to the heterogeneity of exosomes. In this review, we will underline the uses of exosomes as a therapy and their roles in lung regenerative medicine, as well as current challenges in exosome therapies.

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“…Furthermore, most of the intravenously injected MSCs do not reach the target tissues, but rather accumulate in the lungs where they can be phagocytosed by local macrophages that are then stimulated to produce IL10 [26]. On the other hand, MSC local infusion results in high cell mortality by trauma, hypoxia, or NK cells-mediated killing [26]. In summary, in vivo MSC homing appears to be insufficient since only 1% of the infused cells reaches the adequate tissue.…”

Section: Mesenchymal Stromal/stem Cells (Mscs)mentioning

confidence: 99%

“…Endothelial cells could also attract MSCs by producing CXCL12, but MSCs do not express its receptor, CXCR4. On the other hand, in vivo zebrafish analysis with intravital microscopy demonstrates that MSC transmigration takes hours rather than minutes because the cells do not undergo flattening and it occurs through a slow, passive process in which MSCs interact with endothelial cells via integrins [26].…”

Section: Mesenchymal Stromal/stem Cells (Mscs)mentioning

confidence: 99%

Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells

Alfaro

Rodriguez-Sosa

Zapata

2020

JCM

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Mesenchymal stromal/stem cells (MSCs) have emerged as important therapeutic agents, owing to their easy isolation and culture, and their remarkable immunomodulatory and anti-inflammatory properties. However, MSCs constitute a heterogeneous cell population which does not express specific cell markers and has important problems for in vivo homing, and factors regulating their survival, proliferation, and differentiation are largely unknown. Accordingly, in the present article, we review the current evidence on the relationships between Eph kinase receptors, their ephrin ligands, and MSCs. These molecules are involved in the adult homeostasis of numerous tissues, and we and other authors have demonstrated their expression in human and murine MSCs derived from both bone marrow and adipose tissue, as well as their involvement in the MSC biology. We extend these studies providing new results on the effects of Eph/ephrins in the differentiation and immunomodulatory properties of MSCs.

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Myths, reality and future of mesenchymal stem cell therapy

Cited by 23 publications

References 99 publications

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

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

Exosome therapeutics for lung regenerative medicine

Eph/ephrin Signaling and Biology of Mesenchymal Stromal/Stem Cells

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