Autologous decellularized extracellular matrix protects against H2O2-induced senescence and aging in adipose-derived stem cells and stimulates proliferation in vitro

Abstract

Background: Adipose-derived stem cells have attracted significant interest, especially in stem cell therapy and regenerative medicine. However, these cells undergo gradual premature senescence in long-term cultures, which are essential for clinical applications that require cell-assisted lipotransfer or tissue repair. Methods: Since the extracellular matrix forms the microenvironment around stem cells in vitro and regulates self-renewal and multipotency in part by slowing down stem cell aging, we evaluated its potential to protect against senescence, using H2O2-induced adipose-derived stem cells as a model. Results: We found that supplementing cultures with decellularized extracellular matrix harvested from the same cells significantly promotes proliferation and reverses signs of senescence, including decreased multipotency, increased expression of senescence-associated β-galactosidase, and accumulation of reactive oxygen species. Conclusion: These findings suggest a novel approach in which an autologous decellularized extracellular matrix is used to prevent cellular senescence to enable the use of adipose-derived stem cells in regenerative medicine.

Effects of Human and Porcine Adipose Extracellular Matrices Decellularized by Enzymatic or Chemical Methods on Macrophage Polarization and Immunocompetence

“…In the same way, a significant decrease in the percentage of cell population with a high ROS content was also observed when macrophages were cultured on hDAM2, pDAM1, and pDAM2. These results suggest a protective role of these DAMs against oxidative stress, in agreement with other authors [ 44 ].…”

Autologous decellularized extracellular matrix promotes adipogenic differentiation of adipose derived stem cells in low serum culture system by regulating the ERK1/2-PPARγ pathway

“…In our previous work, observation of d-ECM using a scanning electron microscope revealed a fibrous structure that was made up of many cords with the same direction [ 22 ]. In this study, we also noticed a similar structure under an inverted microscopes ( Figure 2(a )).…”

“…It was demonstrated in our previous study that the d-ECM substrate could protect ADSCs against H 2 O 2 -induced senescence and stimulate cell proliferation [ 22 ]. As a natural substance secreted by autologous cells, d-ECM is very safe and has tremendous potential for usage in regeneration medicine [ 28 ].…”

“…The extracellular matrix deposited by ADSCs was obtained according to the scheme we established before [ 22 ]. Briefly, ADSCs were collected and seeded at a density of 1 × 10 5 or 5x10 4 /well in 12- or 24-well plates (Corning, USA) in complete medium.…”

“…It was also reported that ECM fabricated by small intestinal submucosa promoted cell proliferation and osteoblastic differentiation of rat BMSCs through Smad1/5/8 and ERK1/2 signalling pathways [ 21 ]. Moreover, our previous study reported that autologous decellularized extracellular matrix (d-ECM) not only increased the viability but enhanced adipogenic differentiation of ADSCs exposed to H2O2 [ 22 ]. However, whether ERK1/2 pathway is involved in the adipogenic process of ADSCs reseeded on d-ECM still remains unclear.…”