2. Academic Validation
  3. Quality Control of Fetal Wharton's Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles

Quality Control of Fetal Wharton's Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles

  • Int J Nanomedicine. 2025 Feb 11:20:1807-1820. doi: 10.2147/IJN.S497586.
Illayaraja Krishnan 1,  Chiew Yong Ng 1,  Li Ting Kee 1,  Min Hwei Ng 1,  Jia Xian Law 1,  Thavachelvi Thangarajah 2,  Ani Amelia Zainuddin 3,  Zalina Mahmood 4,  Shathiya Rajamanickam 5,  Baskar Subramani 5,  Yogeswaran Lokanathan 1 6
Affiliations

Affiliations

  • 1 Department of Tissue Engineering and Regenerative Medicine (DTERM), Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur, Malaysia.
  • 2 Department of Obstetrics and Gynaecology, Hospital Angkatan Tentera (HAT) Tuanku Mizan, Kuala Lumpur, Malaysia.
  • 3 Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras, Kuala Lumpur, Malaysia.
  • 4 Production and Blood Supply Management Division, National Blood Centre, Kuala Lumpur, Malaysia.
  • 5 Medixcell Sdn. Bhd., Kuala Lumpur, Malaysia.
  • 6 Advance Bioactive Materials-Cells UKM Research Group, Universiti Kebangsaan Malaysia, Bangi, Selangor, Malaysia.
PMID: 39963415 DOI: 10.2147/IJN.S497586
Abstract

Background: Quality control (QC) is an important element in ensuring drug substances' safety, efficacy, and quality. The dosing regimen for sEVs can be in the form of protein concentration or the number of particles based on the results of a series of quality controls applied as in-process control.

Methods: Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were isolated from four independent umbilical cord samples and were characterized following the International Society for Cellular Therapy (ISCT) guidelines. Small extracellular vesicles (sEVs) were isolated separately from these four WJMSCs samples using the Tangential Flow Filtration (TFF) method and were characterized per Minimal Information for Studies of Extracellular Vesicles (MISEV2018) guidelines. Each isolated and concentrated sEV preparation was standardized and its purity was determined by the ratio of the number of particles to protein concentration.

Results: All the WJMSCs samples passed the Mesenchymal Stem Cells (MSCs) characterization QC tests. Qualitatively, EVs-positive markers (CD63 and TSG101) and intact bilipid membrane vesicles were detected in all the sEV preparations. Quantitatively, the protein and particle concentrations revealed that all the sEV preparations were "impure" with < 1.5 × 109 particles/µg protein. Albumin was co-isolated in all the sEV preparations.

Conclusion: In short, all characterized and standardized individual and pooled sEV preparations were deemed "impure" due to albumin co-isolation using the TFF method. For therapeutic development, it is essential to report protein and particle concentrations in EV preparations based on these QC results.

Keywords

Wharton’s jelly mesenchymal stem cells; purity; quality control; small extracellular vesicles; tangential flow filtration; umbilical cord.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-E70005A
    Zinc peptidase, Matrix metalloproteinases (MMPs)
    MMP