Abstract

© 2020 International Society for Cell & Gene Therapy Background aim: Mesenchymal stromal cells (MSCs) hold promise for the treatment of tissue damage and injury. However, MSCs comprise multiple subpopulations with diverse properties, which could explain inconsistent therapeutic outcomes seen among therapeutic attempts. Recently, the adenosine triphosphate-binding cassette transporter ABCB5 has been shown to identify a novel dermal immunomodulatory MSC subpopulation. Methods: The authors have established a validated Good Manufacturing Practice (GMP)-compliant expansion and manufacturing process by which ABCB5+ MSCs can be isolated from skin tissue and processed to generate a highly functional homogeneous cell population manufactured as an advanced therapy medicinal product (ATMP). This product has been approved by the German competent regulatory authority to be tested in a clinical trial to treat therapy-resistant chronic venous ulcers. Results: As of now, 12 wounds in nine patients have been treated with 5 × 105 autologous ABCB5+ MSCs per cm2 wound area, eliciting a median wound size reduction of 63% (range, 32–100%) at 12 weeks and early relief of pain. Conclusions: The authors describe here their GMP- and European Pharmacopoeia-compliant production and quality control process, report on a pre-clinical dose selection study and present the first in-human results. Together, these data substantiate the idea that ABCB5+ MSCs manufactured as ATMPs could deliver a clinically relevant wound closure strategy for patients with chronic therapy-resistant wounds.

RAS ID

38904

Document Type

Journal Article

Date of Publication

2021

ISSN

14653249

School

School of Medical and Health Sciences

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Publisher

Elsevier

Comments

Kerstan, A., Niebergall-Roth, E., Esterlechner, J., Schröder, H. M., Gasser, M., Waaga-Gasser, A. M., ... Kluth, M. A. (2021). Ex vivo-expanded highly pure ABCB5+ mesenchymal stromal cells as good manufacturing practice-compliant autologous advanced therapy medicinal product for clinical use: Process validation and first in-human data. Cytotherapy, 23(2) 165 - 175. https://doi.org/10.1016/j.jcyt.2020.08.012

Share

 
COinS
 

Link to publisher version (DOI)

10.1016/j.jcyt.2020.08.012