The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties?
Open accessAbstract
We have recently reported that therapeutic mesenchymal stromal cells (MSCs) have low engraftment and trigger the instant blood mediated inflammatory reaction (IBMIR) after systemic delivery to patients, resulting in compromised cell function. In order to optimize the product, we compared the immunomodulatory, blood regulatory, and therapeutic properties of freeze-thawed and freshly harvested cells. We found that freeze-thawed MSCs, as opposed to cells harvested from continuous cultures, have impaired immunomodulatory and blood regulatory properties. Freeze-thawed MSCs demonstrated reduced responsiveness to proinflammatory stimuli, an impaired production of anti-inflammatory mediators, increased triggering of the IBMIR, and a strong activation of the complement cascade compared to fresh cells. This resulted in twice the efficiency in lysis of thawed MSCs after 1 hour of serum exposure. We found a 50% and 80% reduction in viable cells with freshly detached as opposed to thawed in vitro cells, indicating a small benefit for fresh cells. In evaluation of clinical response, we report a trend that fresh cells, and cells of low passage, demonstrate improved clinical outcome. Patients treated with freshly harvested cells in low passage had a 100% response rate, twice the response rate of 50% observed in a comparable group of patients treated with freeze-thawed cells at higher passage. We conclude that cryobanked MSCs have reduced immunomodulatory and blood regulatory properties directly after thawing, resulting in faster complement-mediated elimination after blood exposure. These changes seem to be paired by differences in therapeutic efficacy in treatment of immune ailments after hematopoietic stem cell transplantation. Stem Cells 2014;32:2430–2442
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Complement: a key system for immune surveillance and homeostasis
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Mesenchymal stem cells: immune evasive, not immune privileged
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Mesenchymal Stem Cells: Mechanisms of Inflammation
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Shattering barriers toward clinically meaningful MSC therapies
Levy, O., Kuai, R., Siren, E. M. J., Bhere, D., Milton, Y., Nissar, N., De Biasio, M., Heinelt, M., Reeve, B., Abdi, R., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba6884 · Cited by 694
Biological functions of mesenchymal stem cells and clinical implications
Naji, A., Eitoku, M., Favier, B., Deschaseaux, F., Rouas-Freiss, N., & Suganuma, N. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03125-1 · Cited by 624
Moll, G., Ankrum, J. A., Kamhieh-Milz, J., Bieback, K., Ringdén, O., Volk, H.-D., Geissler, S., & Reinke, P. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.12.006 · Cited by 440
Self-citationMarquez-Curtis, L. A., Janowska-Wieczorek, A., McGann, L. E., & Elliott, J. A. W. (2015) · Cryobiology · doi:10.1016/j.cryobiol.2015.07.003 · Cited by 346
The multiple functional roles of mesenchymal stem cells in participating in treating liver diseases
Liu, W., Song, F., Ren, L., Guo, W., Wang, T., Feng, Y., Tang, L., & Li, K. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12482 · Cited by 139
Metadata
- Authors
- Moll, G., Alm, J. J., Davies, L. C., von Bahr, L., Heldring, N., Stenbeck-Funke, L., Hamad, O. A., Hinsch, R., Ignatowicz, L., Locke, M., Lönnies, H., Lambris, J. D., Teramura, Y., Nilsson-Ekdahl, K., Nilsson, B., & Blanc, K.
- Venue
- Stem Cells
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-18
- Volume
- 32
- Issue
- 9
- Pages
- 2430-2442
- ISSN
- 1066-5099 (ISSN-L)
- 1549-4918
- OpenAlex
- W2116259052
- Cited by
- 381
- References
- 41
- FWCI
- 12.60
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Moll, G., Alm, J. J., Davies, L. C., von Bahr, L., Heldring, N., Stenbeck-Funke, L., Hamad, O. A., Hinsch, R., Ignatowicz, L., Locke, M., Lönnies, H., Lambris, J. D., Teramura, Y., Nilsson-Ekdahl, K., Nilsson, B., & Blanc, K. (2014). Do Cryopreserved Mesenchymal Stromal Cells Display Impaired Immunomodulatory and Therapeutic Properties? Stem Cells. https://doi.org/10.1002/stem.1729
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