Advanced

Cryopreserved or fresh mesenchymal stromal cells : Only a matter of taste or key to unleash the full clinical potential of MSC therapy?

Moll, Guido; Geißler, Sven; Catar, Rusan; Ignatowicz, Lech LU ; Hoogduijn, Martin J.; Strunk, Dirk; Bieback, Karen and Ringdén, Olle (2016) In Advances in Experimental Medicine and Biology 951. p.77-98
Abstract

Mesenchymal stromal cells (MSCs) harbor great therapeutic potential for numerous diseases. From early clinical trials, success and failure analysis, bench-to-bedside and back-to-bench approaches, there has been a great gain in knowledge, still leaving a number of questions to be answered regarding optimal manufacturing and quality of MSCs for clinical application. For treatment of many acute indications, cryobanking may remain a prerequisite, but great uncertainty exists considering the therapeutic value of freshly thawed (thawed) and continuously cultured (fresh) MSCs. The field has seen an explosion of new literature lately, outlining the relevance of the topic. MSCs appear to have compromised immunomodulatory activity directly after... (More)

Mesenchymal stromal cells (MSCs) harbor great therapeutic potential for numerous diseases. From early clinical trials, success and failure analysis, bench-to-bedside and back-to-bench approaches, there has been a great gain in knowledge, still leaving a number of questions to be answered regarding optimal manufacturing and quality of MSCs for clinical application. For treatment of many acute indications, cryobanking may remain a prerequisite, but great uncertainty exists considering the therapeutic value of freshly thawed (thawed) and continuously cultured (fresh) MSCs. The field has seen an explosion of new literature lately, outlining the relevance of the topic. MSCs appear to have compromised immunomodulatory activity directly after thawing for clinical application. This may provide a possible explanation for failure of early clinical trials. It is not clear if and how quickly MSCs recover their full therapeutic activity, and if the “cryo stun effect” is relevant for clinical success. Here, we will share our latest insights into the relevance of these observations for clinical practice that will be discussed in the context of the published literature. We argue that the differences of fresh and thawed MSCs are limited but significant. A key issue in evaluating potency differences is the time point of analysis after thawing. To date, prospective double-blinded randomized clinical studies to evaluate potency of both products are lacking, although recent progress was made with preclinical assessment. We suggest refocusing therapeutic MSC development on potency and safety assays with close resemblance of the clinical reality.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Cell engraftment, Cell therapy, Coagulation, Complement, Cryopreservation, Cryopreservation-induced cell death, Freeze injury, Freezethawing, Mesenchymal stromal cell, T cells
in
Advances in Experimental Medicine and Biology
volume
951
pages
22 pages
publisher
Springer New York LLC
external identifiers
  • scopus:84995394520
  • wos:000400699700008
ISSN
00652598
22148019
DOI
10.1007/978-3-319-45457-3_7
language
English
LU publication?
yes
id
ead72605-4b53-43a9-a764-47471abd79f4
date added to LUP
2016-12-06 09:03:47
date last changed
2017-10-22 05:23:11
@inbook{ead72605-4b53-43a9-a764-47471abd79f4,
  abstract     = {<p>Mesenchymal stromal cells (MSCs) harbor great therapeutic potential for numerous diseases. From early clinical trials, success and failure analysis, bench-to-bedside and back-to-bench approaches, there has been a great gain in knowledge, still leaving a number of questions to be answered regarding optimal manufacturing and quality of MSCs for clinical application. For treatment of many acute indications, cryobanking may remain a prerequisite, but great uncertainty exists considering the therapeutic value of freshly thawed (thawed) and continuously cultured (fresh) MSCs. The field has seen an explosion of new literature lately, outlining the relevance of the topic. MSCs appear to have compromised immunomodulatory activity directly after thawing for clinical application. This may provide a possible explanation for failure of early clinical trials. It is not clear if and how quickly MSCs recover their full therapeutic activity, and if the “cryo stun effect” is relevant for clinical success. Here, we will share our latest insights into the relevance of these observations for clinical practice that will be discussed in the context of the published literature. We argue that the differences of fresh and thawed MSCs are limited but significant. A key issue in evaluating potency differences is the time point of analysis after thawing. To date, prospective double-blinded randomized clinical studies to evaluate potency of both products are lacking, although recent progress was made with preclinical assessment. We suggest refocusing therapeutic MSC development on potency and safety assays with close resemblance of the clinical reality.</p>},
  author       = {Moll, Guido and Geißler, Sven and Catar, Rusan and Ignatowicz, Lech and Hoogduijn, Martin J. and Strunk, Dirk and Bieback, Karen and Ringdén, Olle},
  issn         = {00652598},
  keyword      = {Cell engraftment,Cell therapy,Coagulation,Complement,Cryopreservation,Cryopreservation-induced cell death,Freeze injury,Freezethawing,Mesenchymal stromal cell,T cells},
  language     = {eng},
  month        = {11},
  pages        = {77--98},
  publisher    = {Springer New York LLC},
  series       = {Advances in Experimental Medicine and Biology},
  title        = {Cryopreserved or fresh mesenchymal stromal cells : Only a matter of taste or key to unleash the full clinical potential of MSC therapy?},
  url          = {http://dx.doi.org/10.1007/978-3-319-45457-3_7},
  volume       = {951},
  year         = {2016},
}