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MSC biology and clinical use

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 extremely promising immunosuppressive therapeutic agent in severe immunological complications such as graft-versus-host disease. MSCs are also being explored in cell-based therapies for different tissue injuries such as cartilage repair.

Research concerning MSC manufacturing methods

The frequency of MSCs is extremely low in vivo (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. We are currently investigating different strategies to improve our current manufacturing method and the potential impact of cell freezing.

Selected reference:
Eichler H, Schrezenmeier H., Schmallmoser K., Strunk D., Nystedt J., Kaartinen T., Korhonen M., Fleury-Cappellesso S., Sensebé L., Bönig H., Rebulla P., Giordano R., Lecchi L., Takanashi M., Watt S. M., Austin E. B., Guttridge M., McLaughlin L. S., Panzer S. & Reesink H. W.. Donor selection and release criteria of cellular therapy products. Vox Sanguinis 2013;104(1):67-91. PM: 23252690 

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 2015 in press. PM: 25777046

Skog M, Muhonen V, Nystedt J, Narcisi R, Kontturi LS, Urtti A, Korhonen M, van Osch GJ, Kiviranta I. Xeno-free chondrogenesis of bone marrow mesenchymal stromalcells: towards clinical-grade chondrocyte production. Cytotechnology. 2015;67(5):905-19. PM: 24718835

Contact person: Dr Johanna Nystedt, Adj Prof, PhD johanna.nystedt [at] bloodservice.fi


 

Preclinical and clinical MSC research 

We are pursuing active preclinical research concerning the use of MSCs in tissue injury and inflammation such as stroke, cartilage defects and colitis and in active collaboration with experts in the field. We also conduct active clinical MSC research, especially concerning their use in graft-versus-host disease (GvHD), in collaboration with Finnish clinicians.

Selected references:

Mitkari B, Kerkelä E, Nystedt J, Korhonen M, Mikkonen V, Huhtala T, Jolkkonen J. Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats. Exp Neurol. 2013; 239C:158-62. PM: 23059455

Mitkari B, Kerkelä, E, Nystedt J, Korhonen M, Jolkkonen J. Unexpected complication in a rat stroke model - Exacerbation of secondary pathology in the thalamus by subacute intra-arterial administration of human bone marrow derived mesenchymal stem cells.  Journal of Cerebral Blood Flow & Metabolism 2015;35(3):363-6. PM: 25564231

Muhonen V, Narcisi R, Nystedt J, Korhonen M, van Osch GJ, 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. J Tissue Eng Regen Med. 2015 in press. PM:  25643647

Contact persons:

Dr. Johanna Nystedt

Dr. Matti Korhonen

 

MSC biology

We have produced over 30 peer-reviewed publications concerning mesenchymal stromal/stem cell (MSC) research with focus areas on e.g. MSC biodistribution and targeting and MSC markers.

Selected references:

Kerkelä E, Hakkarainen T, Mäkelä T, Raki M, Kampur O, Kilpinen L, Nikkilä J, Lehtonen S, Ritamo I, Pernu R, Pietilä M, Takalo R, Juvonen T, Bergström K, Kalso E, Valmu L, Laitinen S, Lehenkari P, Nystedt J. Transient Proteolytic Modification of Mesenchymal Stromal Cells Increases Lung Clearance Rate and Targeting to Injured Tissue. Stem Cells Transl Med. 2013;2(7):510-20. (inaugural IF 3.596). PM: 23734061

Nystedt J, Anderson H, Hirvonen T, Impola U, Jaatinen T, Heiskanen A, Blomqvist M, Satomaa T, Natunen J, Saarinen J, Lehenkari P, Valmu L, Laine J. Human CMP-N-acetylneuraminic acid hydroxylase is a novel stem cell marker linked to stem cell-specific mechanisms. Stem Cells. 2010;28(2):258-67. (IF 7.781). PM: 19890979

Nystedt J, Anderson H, Tikkanen J, Pietilä M, Hirvonen T, Takalo R, Heiskanen A, Satomaa T, Natunen S, Lehtonen S, Hakkarainen T, Korhonen M, Laitinen S, Valmu L, Lehenkari P. Cell surface structures influence lung clearance rate of systemically infused mesenchymal stromal cells. Stem Cells 2013;31(2):317-26. (IF 7.781). PM: 23132820

Contact persons:

Dr Johanna Nystedt, Adj Prof, PhD; email: johanna.nystedt(at)bloodservice.fi

Dr. Matti Korhonen, Adj Prof, PhD; email: matti.korhonen(at)bloodservice.fi