Abstract
To date, the therapeutic efficacy of human mesenchymal stem cells (hMSCs) has been investigated in various clinical trials with moderate or, in some cases, inconsistent results. The still elusive reproducibility relates, in part, with constitutive differences in the cell preparation, translated into variable cell potencies. Other factors include poor cell homing and survival, and age-/disease-associated host tissue impairment. It is well accepted that within in vivo niches, MSCs exist as heterogeneous cell populations with different stemness propensities and supportive functions. Phenotype-based MSC purification of homogeneous subsets can result in cell populations with distinct biological functions. In addition, preclinical studies have shown that MSC functionalization in vitro, through cell priming, can boost their immunomodulatory, trophic, and reparative capacities in vivo. Therefore, in this review, we discuss how phenotype-based MSC purification and MSC priming technologies can contribute to an improved MSC-based product for safer and more effective therapeutic applications. Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to inherent interdonor variability, negatively impact the standardization and reproducibility of their therapeutic potential. The identification of innate distinct functional MSC subpopulations, as well as the description of ex vivo protocols aimed at maintaining phenotypes and enhancing specific functions have the potential to overcome these limitations. The incorporation of those approaches into cell-based therapy would significantly impact the field, as more reproducible clinical outcomes may be achieved.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 55-77 |
| Number of pages | 23 |
| Journal | Tissue Engineering - Part B: Reviews |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 1 2019 |
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Keywords
- cell priming
- cellular phenotypes
- mesenchymal stem cells
- MSC subpopulations
ASJC Scopus subject areas
- Bioengineering
- Biomaterials
- Biochemistry
- Biomedical Engineering
Cite this
Mesenchymal Stem Cell Functionalization for Enhanced Therapeutic Applications. / Kouroupis, Dimitrios; Sanjurjo-Rodriguez, Clara; Jones, Elena; Correa, Diego.
In: Tissue Engineering - Part B: Reviews, Vol. 25, No. 1, 01.02.2019, p. 55-77.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Mesenchymal Stem Cell Functionalization for Enhanced Therapeutic Applications
AU - Kouroupis, Dimitrios
AU - Sanjurjo-Rodriguez, Clara
AU - Jones, Elena
AU - Correa, Diego
PY - 2019/2/1
Y1 - 2019/2/1
N2 - To date, the therapeutic efficacy of human mesenchymal stem cells (hMSCs) has been investigated in various clinical trials with moderate or, in some cases, inconsistent results. The still elusive reproducibility relates, in part, with constitutive differences in the cell preparation, translated into variable cell potencies. Other factors include poor cell homing and survival, and age-/disease-associated host tissue impairment. It is well accepted that within in vivo niches, MSCs exist as heterogeneous cell populations with different stemness propensities and supportive functions. Phenotype-based MSC purification of homogeneous subsets can result in cell populations with distinct biological functions. In addition, preclinical studies have shown that MSC functionalization in vitro, through cell priming, can boost their immunomodulatory, trophic, and reparative capacities in vivo. Therefore, in this review, we discuss how phenotype-based MSC purification and MSC priming technologies can contribute to an improved MSC-based product for safer and more effective therapeutic applications. Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to inherent interdonor variability, negatively impact the standardization and reproducibility of their therapeutic potential. The identification of innate distinct functional MSC subpopulations, as well as the description of ex vivo protocols aimed at maintaining phenotypes and enhancing specific functions have the potential to overcome these limitations. The incorporation of those approaches into cell-based therapy would significantly impact the field, as more reproducible clinical outcomes may be achieved.
AB - To date, the therapeutic efficacy of human mesenchymal stem cells (hMSCs) has been investigated in various clinical trials with moderate or, in some cases, inconsistent results. The still elusive reproducibility relates, in part, with constitutive differences in the cell preparation, translated into variable cell potencies. Other factors include poor cell homing and survival, and age-/disease-associated host tissue impairment. It is well accepted that within in vivo niches, MSCs exist as heterogeneous cell populations with different stemness propensities and supportive functions. Phenotype-based MSC purification of homogeneous subsets can result in cell populations with distinct biological functions. In addition, preclinical studies have shown that MSC functionalization in vitro, through cell priming, can boost their immunomodulatory, trophic, and reparative capacities in vivo. Therefore, in this review, we discuss how phenotype-based MSC purification and MSC priming technologies can contribute to an improved MSC-based product for safer and more effective therapeutic applications. Culture expansion of MSCs has detrimental effects on various cell characteristics and attributes (e.g., phenotypic changes and senescence), which, in addition to inherent interdonor variability, negatively impact the standardization and reproducibility of their therapeutic potential. The identification of innate distinct functional MSC subpopulations, as well as the description of ex vivo protocols aimed at maintaining phenotypes and enhancing specific functions have the potential to overcome these limitations. The incorporation of those approaches into cell-based therapy would significantly impact the field, as more reproducible clinical outcomes may be achieved.
KW - cell priming
KW - cellular phenotypes
KW - mesenchymal stem cells
KW - MSC subpopulations
UR - http://www.scopus.com/inward/record.url?scp=85061562416&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061562416&partnerID=8YFLogxK
U2 - 10.1089/ten.teb.2018.0118
DO - 10.1089/ten.teb.2018.0118
M3 - Review article
C2 - 30165783
AN - SCOPUS:85061562416
VL - 25
SP - 55
EP - 77
JO - Tissue Engineering - Part B: Reviews
JF - Tissue Engineering - Part B: Reviews
SN - 1937-3368
IS - 1
ER -