MSC clinical use and therapeutic mechanisms

Mesenchymal stromal/stem cells (MSCs) are multipotent adult cells which can be isolated from several adult tissues. MSCs have been explored in tissue repair due to their differentiation potential into mesenchymal lineages. Besides their regenerative capacities, MSCs also display immunomodulatory functions and with very low immunogenicity. For these reasons, MSCs are emerging as an interesting and promising immunosuppressive therapeutic agent in severe immunological complications such as for instance graft-versus-host disease. MSCs are also being explored in cell-based therapies for different tissue injuries.

We are engaged in several clinical research collaborations exploring the use of allogeneic bone marrow-derived mesenchymal stromal cells (MSCs) in refractory graft-versus-host disease, a life-threatening complication after stem cell transplantations. We are also interested in elucidating the therapeutic mechanisms of MSCs, especially in immunomodulation. We are also interested in potential new clinical indications for MSCs such as autoimmune diseases, stroke, cartilage defects and colitis in active collaboration with experts in the field.

The frequency of MSCs is extremely low in adult tissues (for instance 0.001–0.01% of all nucleated cells in the bone marrow) and an ex vivo expansion (cell culture) step is thus inevitable to obtain sufficient cell numbers for research or clinical purposes. We are engaged in research concerning clinical MSC manufacturing, especially the development of xenofree (animal-component free) cell culture methods. A GMP- and clinically-compliant cell culture method has been developed in-house for bone marrow-derived MSCs.

Anita Laitinen

Production Manager, PhD

Selected references:

Salmenkari H, Laitinen A, Forsgård R, Holappa M, Lindén J, Pasanen L, Korhonen M, Korpela R and Nystedt J. The utilization of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis: a preclinical study. Cytotherapy 2019 Epub Jan 2. pii: S1465-3249(18)30703-5. PMID: 30611671

Keto J, Kaartinen T, Salmenniemi U, Castrén J, Partanen J, Hänninen A, Korhonen M, Lähteenmäki K, Itälä-Remes M, Nystedt J. Immunomonitoring of MSC-Treated GvHD Patients Reveals Only Moderate Potential for Response Prediction but Indicates Treatment Safety. Mol Ther Methods Clin Dev. 2018 Feb 8;9:109-118. PMID: 29516024

Oja S, Komulainen P, Penttilä A, Nystedt J, Korhonen M. Automated image analysis detects aging in clinical-grade mesenchymal stromal cell cultures. Stem Cell Res Ther. 2018 Jan 10;9(1):6. PMID: 29321040

Muhonen V, Narcisi R, Nystedt J, Korhonen M, van Osch GJ and Kiviranta I. Recombinant human type II collagen hydrogel provides a xeno-free 3D micro-environment for chondrogenesis of human bone marrow-derived mesenchymal stromal cells. Journal of Tissue Engineering and Regenerative Medicine 2017;11(3):843-54. PMID: 25643647

Salmenniemi U, Itälä-Remes M, Nystedt J, Putkonen M, Niittyvuopio R, Vettenranta K, Korhonen M. Good responses but high TRM in adult patients after MSC therapy for GvHD. Bone Marrow Transplantation 2017;52(4):606-8. PMID: 27941780

Strunk D, Lozano M, Marks DC, Loh YS, Gstraunthaler G, Schennach H, Rohde E, Laner-Plamberger S, Öller M, Nystedt J, Lotfi R, Rojewski M, Schrezenmeier H, Bieback K, Schäfer R, Bakchoul T, Waidmann M, Jonsdottir-Buch SM, Montazeri H, Sigurjonsson OE, Iudicone P, Fioravanti D, Pierelli L, Introna M, Capelli C, Falanga A, Takanashi M, Lόpez-Villar O, Burnouf T, Reems JA, Pierce J, Preslar AM, Schallmoser K. International Forum on GMP-grade human platelet lysate for cell propagation: summary. Vox Sang. 2017 Oct 26. PMID: 29076169

Laitinen A, Oja S, Kilpinen L, Kaartinen T, Möller J, Laitinen S, Korhonen M, Nystedt J. A robust and reproducible animal serum-free culture method for clinical-grade bone marrow-derived mesenchymal stromal cells. Cytotechnology 2016;68(4):891-906. PMID: 25777046

Mitkari B, Nitzsche F, Kerkelä E, Kuptsova K, Huttunen J, Nystedt J, Korhonen M, Jolkkonen J. Human bone marrow mesenchymal stem/stromal cells produce efficient localization in the brain and enhanced angiogenesis after intra-arterial delivery in rats with cerebral ischemia, but this is not translated to behavioral recovery. Behav Brain Res. 2014; 259:50-59. PMID: 24177208