The study investigates the effects of Thymosin Beta 4 (Tβ4) on the viability and function of adipose-derived stem cells (ADSCs) in enhancing the success of autologous fat grafting (AFG). Findings indicate that Tβ4 significantly promotes ADSC proliferation and reduces apoptosis, potentially improving fat cell survival and retention post-transplantation. Additionally, Tβ4 influences angiogenesis-related gene expression and the Hippo signaling pathway, suggesting its role as a positive regulator of ADSC activity in AFG procedures.
Autologous fat grafting is primarily utilized in aesthetic and plastic surgeries to replenish soft tissue deficiencies and enhance the recipient’s appearance. The technique is favored for several reasons, such as: adipose tissue can be harvested from the patient’s own body, providing a natural source of material for grafting; the harvested fat can be used in a variety of anatomical areas to enhance volume and contour; the minimally invasive nature of fat harvesting tends to result in less trauma compared to other methods that might involve implants or foreign materials; since the fat is autologous, there is a minimal risk of immune rejection compared to transplanted tissues from donors. Despite these advantages, the success of fat grafting can be affected by variable survival rates of the grafted fat, highlighting the need for techniques to enhance fat retention, such as the potential role of Tβ4 in promoting adipose-derived stem cell viability.
Thymosin Beta 4 plays a significant role in facilitating the differentiation of adipose-derived stem cells into endothelial cells (ECs). The study indicates that Tβ4-treated ADSCs have shown tendencies to differentiate into ECs without needing special induction media. Specifically, Tβ4 enhances the expression of important angiogenesis-related genes such as ANGPT1 and TEK, which are critical for promoting EC survival and function. The increased ratio of ANGPT1 to ANGPT2 in Tβ4-treated cells suggests that Tβ4 effectively promotes angiogenesis by favoring a stable vascular environment.
Furthermore, the study observes that Tβb4 upregulates TEK expression in ADSCs, indicating a predisposition towards differentiation into ECs. Importantly, it has been noted that Tβ4 may induce the differentiation of ADSCs into ECs via the Hippo pathway, as the expression levels of key genes involved in this pathway, such as YAP1 and CCN2, were significantly altered in the presence of Tβ4.
The expression of angiogenic factors in Tβ4-treated adipose-derived stem cells shows notable changes compared to control groups. The mRNA expression of ANGPT1 was significantly elevated in the Tβ4-treated groups. In contrast, the expression of ANGPT2 decreased in the Tβ4-treated groups, indicating that Tβ4 may help shift the balance favoring angiogenesis by decreasing this antagonist factor. Although there was no statistically significant difference in the mRNA expression of VEGFA among the groups, the data indicated a tendency for increased expression in the Tβ4-treated groups compared to the control.
The Hippo signaling pathway plays a crucial role in regulating adipose-derived stem cells in relation to the effects of Thymosin Beta 4. This pathway is known for its impact on self-renewal and stemness properties of stem cells, primarily through its effectors, YAP (Yes-associated protein) and WWTR1 (WW domain-containing transcription regulator 1). When the Hippo pathway is inactive, unphosphorylated YAP/WWTR1 translocates to the nucleus and activates transcription factors, which in turn enhances the expression of target genes such as CCN2 (Cell Communication Network Factor 2) that are involved in crucial processes like cell adhesion, proliferation, differentiation, and angiogenesis.
The findings on Thymosin Beta 4 and its effect on adipose-derived stem cell migration have several implications for future research. First, the study indicates that while Tβ4 did not show a significant impact on ADSC migration in the wound healing assay, there are notable discrepancies with previous studies that suggested Tβ4 could enhance migration under different conditions. This highlights the need for further investigations to reconcile these conflicting results and to comprehend the conditions under which Tβ4 may affect ADSC migration.
The researchers noted that variations in experimental setups, such as observation time spans and the cellular environment, could contribute to the differences observed. Therefore, future research should explore different parameters such as concentration, incubation time, and possibly the specific types of ADSCs used to evaluate their migratory behavior in response to Tβ4. Additionally, this approach could enhance the understanding of how ADSCs interact with their microenvironment during fat grafting procedures.
Furthermore, since cellular heterogeneity may have influenced the results, it suggests the necessity for larger-scale studies and varied models to determine the precise mechanisms behind ADSC migration and the role of Tβ4. Investigating the modulation of other pathways and factors that might interact with Tb4 could also yield insights valuable for optimizing therapeutic applications involving ADSCs in autologous fat grafting and other regenerative therapies.
Full article can be found here: https://doi.org/10.1007/s00266-024-03861-1