Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells

Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine known to promote embryonic stem cells survival, is robustly adipogenic and induces postnatal adipose tissue formation in vivo of transplanted adipose stem/progenitor cells (ASCs) and recruited endogenous cells. In vitro, Ptn stimulated human adipose tissue derived ASCs to differentiate into lipid-laden adipocytes by upregulating peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα), with differentiated cells increasingly secreting adiponectin, leptin, glycerol and total triglycerides. Ptn-primed human ASCs seeded in 3D-bioprinted biomaterial scaffolds yielded newly formed adipose tissue that expressed human PPARγ, when transplanted into the dorsum of athymic mice. Remarkably, Ptn-adsorbed 3D scaffolds implanted in the inguinal fat pad had enhanced adipose tissue formation, suggesting Ptn's ability to induce in situ adipogenesis of endogenous cells. Ptn promoted adipogenesis by upregulating PPARγ and C/EBPα not only in adipogenesis induction medium, but also in chemically defined medium specifically for osteogenesis, and concurrently attenuated Runx2 and Osx via BMP-mediated SMAD1/5 phosphorylation. These findings suggest Ptn's novel role as an adipogenesis inducer with a therapeutic potential in soft tissue reconstruction and augmentation.

 

Comments:

The passage you provided describes an experimental study that explores the potential of Pyrintegrin (Ptn) in promoting adipogenesis, the process of forming fat cells, both in vitro and in vivo. Here's a breakdown of the key findings and implications of the study:

1. **Background**: Focal adipose deficiency, which can result from various factors like lipoatrophy (loss of fat tissue), lumpectomy, or facial trauma, is a challenge in reconstructive medicine. However, there is limited research in this area.

2. **Ptn's Effect on Adipose Tissue Formation**: The study found that Pyrintegrin (Ptn), a specific chemical compound, induces the formation of adipose tissue. This effect was observed in both transplanted adipose stem/progenitor cells (ASCs) and the body's own recruited cells.

3. **In Vitro Adipogenesis**: In laboratory settings (in vitro), Ptn stimulated human adipose tissue-derived ASCs to differentiate into mature fat cells (adipocytes). This differentiation was marked by the increased production of specific proteins (peroxisome proliferator-activated receptor (PPARγ) and CCAAT/enhancer-binding protein-α (C/EBPα)) associated with adipocyte development.

4. **Adipose Tissue Formation In Vivo**: When Ptn-primed human ASCs were placed in 3D-bioprinted biomaterial scaffolds and transplanted into mice, new adipose tissue formed. This demonstrates the potential for using Ptn to create adipose tissue in living organisms.

5. **Mechanism of Action**: Ptn promoted adipogenesis by upregulating specific genes (PPARγ and C/EBPα) not only in conditions promoting fat cell development but also when conditions favored osteogenesis (formation of bone tissue). This dual action is notable and suggests a potential therapeutic application.

6. **Therapeutic Implications**: The study suggests that Ptn could be used therapeutically in soft tissue reconstruction and augmentation. This is particularly significant for individuals who have experienced loss of adipose tissue due to various medical procedures or traumas.

7. **In Situ Adipogenesis**: Importantly, the study showed that Ptn could induce the formation of adipose tissue in its native location (in situ) by enhancing the body's natural ability to form fat cells. This could have significant implications for reconstructive surgery where the goal is to restore lost fatty tissue in specific areas.

In summary, this research indicates that Pyrintegrin has the potential to be a valuable tool in reconstructive medicine, particularly for addressing issues related to the loss of adipose tissue. Further studies and clinical trials would be necessary to fully assess its safety and efficacy in human patients.

Related Products

Cat.No.	Product Name	Information
E0462	Pyrintegrin	Pyrintegrin is an β1-integrin agonist and a 2,4-disubstituted pyrimidine that promotes embryonic stem cells survival, also enhances cell-extracellular matrix (ECM) adhesion-mediated integrin signaling.

Related Targets

Integrin