Uc-Msc Derived Small Extracellular Vesicles from Havdi Peptide-Functionalized Nanofibers Potently Induce Chondrogenesis


Taş Z., Ulaşlı A. M., Sunguroğlu A., Yaylacı S., Odabaşı İ., Meral P., ...Daha Fazla

2nd Extracellular Vesicles Conference (TURSEV-26), Ankara, Türkiye, 5 - 06 Haziran 2026, ss.41, (Özet Bildiri)

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Ankara
  • Basıldığı Ülke: Türkiye
  • Sayfa Sayıları: ss.41
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

Mesenchymal stem cells(MSCs) are characterized by high regenerative capacity, potent immunomodulatory properties, and a fibroblast-like

morphology. Among MSC sources, umbilical cord-derived MSCs(UC-MSCs) are considered particularly advantageous due to their high

proliferative potential, low immunogenicity, and strong regenerative efficacy. Extracellular vesicles(EVs) derived from UC-MSCs have

emerged as key mediators of tissue repair, including cartilage regeneration, by transferring bioactive molecules that regulate cellular

communication and differentiation. As the biological significance of UC-MSC-derived EVs has become better understood, their therapeutic

potential in cartilage tissue lesions has gained increasing attention. Previous studies have demonstrated that N-cadherin biomimetic peptides


with high regenerative potential can effectively induce chondrogenic differentiation in UC-MSCs. HAVDI stands for Histidine-Alanine-

Valine-Aspartic acid-Isoleucine, a pentapeptide sequence derived from the first extracellular domain of N-cadherin. However, the downstream


paracrine effects of these biomimetic microenvironments particularly on the composition and function of secreted EVs-remain insufficiently

characterized. In particular, the role of EVs released under N-cadherin-mimetic environment in modulating chondrogenic differentiation has

not been fully elucidated. In this study, UC-MSC-derived EVs were characterized and effects on in vitro chondrogenic differentiation were

systematically investigated using N-cadherin-mimetic peptide nanofiber systems. EVs obtained from four different culture conditions;

conventional two-dimensional (2D) UC-MSC culture, three-dimensional (3D) spheroid culture, 3D HAVDI peptide hydrogel culture, and 3D

scrambled (SCRAM) peptide hydrogel culture-were comparatively analyzed. EVs were isolated from conditioned media and characterized in

terms of particle concentration, size distribution, surface marker expression, and zeta potential. EVs derived from each culture condition were

applied to UC-MSCs undergoing chondrogenic induction at a concentration of 1 × 107 particles per 80,000 cells. The gene expression levels of

key chondrogenic markers (ACAN,SOX9,COL1A1, and COL2A1) were analyzed on days 3 and 10, together with using Safranin O staining.

The results demonstrated that UC-MSC-derived small EVs significantly support chondrogenic differentiation, with EVs obtained from

HAVDI-based biomimetic hydrogels showing the most pronounced effects. Overall, these findings highlight the critical influence of the N-

cadherin biomimetic culture environment on the functional properties of UC-MSC-derived EVs. The results provide a strong foundation for

the development of peptide-based EV therapeutics for cartilage repair and osteochondral regeneration, particularly in age-related degenerative

conditions.