Engineering Human Beige Adipose Tissue

Abstract

In this study, we described a method for generating functional, beige (thermogenic) adipose microtissues from human microvascular fragments (MVFs). The MVFs were isolated from adipose tissue acquired from adults over 50 years of age. The tissues express thermogenic gene markers and reproduce functions essential for the potential therapeutic impact of beige adipose tissues such as enhanced lipid metabolism and increased mitochondrial respiration. MVFs serve as a potential single, autologous source of cells that can be isolated from adult patients, induced to recreate functional aspects of beige adipose tissue and enable rapid vascularization post-transplantation. This approach has the potential to be used as an autologous therapy for metabolic diseases or as a model for the development of a personalized approach to high-throughput drug development/screening for adipose tissue.

Biofabrication of vascularized adipose tissues and their biomedical applications

“…This is because MVFs, including small arterioles, venules and capillaries, are rich in macrophages, T-cells, progenitor cells (white and brown precursors), perivascular stem cells with multidifferentiation potential, myeloid cells, hematopoietic cells, pericytes and ECs? 47,48,188 In a recent study, functional beige AT microtissues were developed by suspending MVFs isolated from human subcutaneous AT in fibrin gel. While the structures cultured in white, beige adipogenic differentiation and growth medium for 14 days showed similar results in terms of vascularization (percentage of well coverage around 0.3 to 0.5%), the structures cultured in beige medium exhibited increased glucose uptake, higher expression of brown related markers (such as UCP1), and gave better results in terms of improved cellular respiration compared to the other groups.…”

“…While the structures cultured in white, beige adipogenic differentiation and growth medium for 14 days showed similar results in terms of vascularization (percentage of well coverage around 0.3 to 0.5%), the structures cultured in beige medium exhibited increased glucose uptake, higher expression of brown related markers (such as UCP1), and gave better results in terms of improved cellular respiration compared to the other groups. 48 In another related report, vascularized beige AT structures were obtained in vitro with MVFs isolated from lean and diabetic rat models and examined in terms of beige and vascularization characteristics. After 14 days of in vitro cultivation, the structures taken from the lean rat caused higher angiogenesis with an interconnected network compared to the MVF group of diabetic origin, regardless of the culture medium.…”

“…While the structures cultured in white, beige adipogenic differentiation and growth medium for 14 days showed similar results in terms of vascularization (percentage of well coverage around 0.3 to 0.5%), the structures cultured in beige medium exhibited increased glucose uptake, higher expression of brown related markers (such as UCP1), and gave better results in terms of improved cellular respiration compared to the other groups. 48…”

“…46 There is no evidence that the thermogenic function of beige adipocytes is ultimately different from classical brown adipocytes, but various in vivo and in vitro studies have suggested that beige adipocytes may also be effective in the treatment of obesity and related comorbidities. [46][47][48][49] 1.1.4. Yellow adipose tissue.…”

Therapeutic Potential of Engineered Beige Adipocytes in Metabolic Diseases

“…Implantation of BAT to replace or supplement white adipose tissue (WAT) using donor brown or beige tissue is impractical due to limited availability (White et al, 2019). Therefore, tissue engineering has been proposed as an alternative method that can produce sufficient volume of autologous beige or brown adipose tissue for clinical treatment (Gonzalez Porras et al, 2022;. In recent studies, functional beige (thermogenic) adipose microtissues have been generated using human microvascular fragments (MVF).…”