Stress-induced senescence in mesenchymal stem cells: Triggers, hallmarks, and current rejuvenation approaches

Lee, S.; Vu, Thi An; Weiss, Anthony S.; Yeo, Giselle C.

doi:10.1016/j.ejcb.2023.151331

Cited by 10 publications

(11 citation statements)

References 235 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A functional network of blood vessels is essential for providing oxygen and nutrients to the regenerating tissue, enabling efficient osseointegration and supporting the viability of transplanted cells. The lack of sufficient vascularisation in a scaffold can lead to oxygen and nutrient deficiency, the accumulation of waste products, and, ultimately, graft failure [ 224 ]. The oxygen diffusion limit of less than 200 μm becomes a critical factor.…”

Section: Vascularisationmentioning

confidence: 99%

“…The induction of angiogenesis in bone defects often involves the use of angiogenic growth factors, including, but not limited to VEGF, FGF, PDGF, TGF, and angiopoietins (Ang) [ 224 , 229 , 235 , 239 ]. These growth factors are commercially available, and incorporation into scaffold constructs or hydrogels is technically straightforward.…”

Section: Vascularisationmentioning

confidence: 99%

“…Growth factors are known to stimulate the migration and proliferation of nearby endothelial cells (ECs), promoting the formation of new blood vessels and establishing a functional vascular network at the defect site. Angiogenic growth factors are often combined with osteogenic growth factors to create a microenvironment that not only supports the differentiation of MSCs into osteogenic lineages but also promotes angiogenesis, leading to the development of a vascular network within the engineered tissue [ 224 , 235 ].…”

Section: Vascularisationmentioning

confidence: 99%

“…The ‘in vivo bioreactor (IVB)’ technique has been widely used to create vascularised tissues before implantation, offering a promising translational approach by harnessing the patient’s body as a bioreactor to prefabricate new vascularised tissues for reconstructive purposes [ 224 , 235 , 251 ]. Chambers, corresponding in shape to the defect, are created at a suitable and healthy location of the patient’s body and implanted with the construct.…”

Section: Vascularisationmentioning

confidence: 99%

See 3 more Smart Citations

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Quek,

Vizetto-Duarte,

Teoh

et al. 2024

JFB

View full text Add to dashboard Cite

The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering—stem cells, scaffolds, the microenvironment, and vascularisation—addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects.

show abstract

Section: Vascularisationmentioning

confidence: 99%

Section: Vascularisationmentioning

confidence: 99%

Section: Vascularisationmentioning

confidence: 99%

Section: Vascularisationmentioning

confidence: 99%

See 2 more Smart Citations

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Quek,

Vizetto-Duarte,

Teoh

et al. 2024

JFB

View full text Add to dashboard Cite

show abstract

“…But it may also lead to tissue necrosis if macrophage apoptosis is not properly coupled with phagocytic clearance [ 9 ]. However, some reports showed that the inflammation and oxidative stress-induced cellular senescence alter the immunomodulatory capacity of MSCs and impede their pro-regenerative function, leading to increased disease severity, maladaptive tissue injury, and development of complications [ 13 , 14 , 15 ]. Whether this age-related dysfunction of MSCs can affect tissue regeneration by altering MSCs’ interaction with macrophages, or more specifically altering the macrophage apoptosis, has not been clearly reported.…”

Section: Introductionmentioning

confidence: 99%

Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression

Zhang,

Akiyama,

Mun

et al. 2024

IJMS

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs’ endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

show abstract

The Matrix Protein Tropoelastin Prolongs Mesenchymal Stromal Cell Vitality and Delays Senescence During Replicative Aging

Lee,

Al Halawani,

Teo

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Cellular senescence leads to the functional decline of regenerative cells such as mesenchymal stromal/stem cells (MSCs), which gives rise to chronic conditions and contributes to poor cell therapy outcomes. Aging tissues are associated with extracellular matrix (ECM) dysregulation, including loss of elastin. However, the role of the ECM in modulating senescence is underexplored. In this work, it is shown that tropoelastin, the soluble elastin precursor, is not only a marker of young MSCs but also actively preserves cell fitness and delays senescence during replicative aging. MSCs briefly exposed to tropoelastin exhibit upregulation of proliferative genes and concurrent downregulation of senescence genes. The seno‐protective benefits of tropoelastin persist during continuous, long‐term MSC culture, and significantly extend the MSC replicative lifespan. Tropoelastin‐expanded MSCs further maintain youth‐associated phenotype and function compared to age‐matched controls, including preserved clonogenic potential, minimal senescence‐associated beta‐galactosidase activity, maintained cell sizes, reduced expression of senescence markers, suppressed secretion of senescence‐associated factors, and increased production of youth‐associated proteins. This work points to the utility of exogenously‐supplemented tropoelastin for manufacturing MSCs that robustly maintain regenerative potential with age. It further reveals the active role of classical structural ECM proteins in driving cellular age‐associated fitness, potentially leading to future interventions for aging‐related pathologies.

show abstract

Stress-induced senescence in mesenchymal stem cells: Triggers, hallmarks, and current rejuvenation approaches

Cited by 10 publications

References 235 publications

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression

The Matrix Protein Tropoelastin Prolongs Mesenchymal Stromal Cell Vitality and Delays Senescence During Replicative Aging

Contact Info

Product

Resources

About