Abstract
The promising field of regenerative medicine is thrilling as it can repair and restore organs for various debilitating diseases. Mesenchymal stem cells are one of the main components in regenerative medicine that work through the release of secretomes. By adopting the use of the secretome in cell-free-based therapy, we may be able to address the challenges faced in cell-based therapy. As one of the components of cell-free-based therapy, secretome has the advantage of a better safety and efficacy profile than mesenchymal stem cells. However, secretome has its challenges that need to be addressed, such as its bioprocessing methods that may impact the secretome content and its mechanisms of action in clinical settings. Effective and standardization of bioprocessing protocols are important to ensure the supply and sustainability of secretomes for clinical applications. This may eventually impact its commercialization and marketability. In this review, the bioprocessing methods and their impacts on the secretome profile and treatment are discussed. This improves understanding of its fundamental aspects leading to potential clinical applications.
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Abbreviations
- Alg:
-
Alginate
- ALI-model:
-
Acute lung injury mice model
- ANGPT1:
-
Angiopoietin-1
- ASC-CCM:
-
Adipose-derived stem cell concentrated conditioned medium
- ASC-S:
-
Adipose tissue-derived stromal cell secretome
- AST-ST:
-
Hypoxic cultured adipose-derived mesenchymal stem cell secretome
- BDNF:
-
Brain-derived neurotrophic factor
- bFGF:
-
Basic fibroblast growth factor
- CG:
-
Carrageenan
- Ch:
-
Chitosan
- CM:
-
Conditioned media
- CNTF:
-
Ciliary neurotrophic factor
- COPD:
-
Chronic obstructive pulmonary disease
- COX2:
-
Cyclooxygenase 2
- CRD:
-
Chronic respiratory disease
- CS:
-
Chondroitin sulfate
- CTGF:
-
Connective tissue growth factor
- CXCL:
-
C-X-C motif chemokine ligand
- DCM:
-
Dilated cardiomyopathy
- dECM:
-
Cardiac decellularized extracellular matrix
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- ECM:
-
Extracellular matrix
- EF-2:
-
Eukaryotic elongation factor 2
- EGF:
-
Epidermal growth factor
- EPO:
-
Erythropoietin
- EPOR:
-
Erythropoietin receptor
- EV:
-
Extracellular vesicle
- FBS:
-
Fetal bovine serum
- FDA:
-
US Food and Drug Administration
- FGF:
-
Fibroblast growth factor
- FLT-3:
-
Fms-related tyrosine kinase 3
- Gal:
-
Galectin
- GDNF:
-
Glial cell-derived neurotrophic factor
- GDNF:
-
Glial-derived neurotrophic factor
- GM-CSF:
-
Granulocyte-macrophage colony-stimulating factor
- GMP:
-
Good manufacturing practice TGF-β1
- HA:
-
Hyaluronic acid
- HGF:
-
Hepatocyte growth factor
- HGF:
-
Hepatocyte growth factor
- HLA-1:
-
Human leukocyte antigen 1
- HLA-G5:
-
Human leukocyte antigen G5
- hNPC:
-
Human neural precursor cells
- HO-1:
-
Heme oxygenase-1
- hPL:
-
Human platelet lysate
- Hypo-CM:
-
Hypoxic cultured human umbilical cord-derived mesenchymal stem cells secretome
- ICAM:
-
Intercellular adhesion molecule
- IDO:
-
Indoleamine 2,3-dioxygenase
- IFN-γ:
-
Interferon gamma
- IGF:
-
Insulin-like growth factors
- IL:
-
Interleukins
- IL18BP:
-
IL18 binding protein
- IL-1Ra:
-
Interleukin-1 receptor antagonist
- iPSC:
-
Human induced pluripotent stem cell
- KGF :
-
Keratinocyte growth factor
- LAP:
-
Latency-associated protein
- LCMS:
-
Liquid chromatography–mass spectrometry
- LCMS:
-
Liquid chromatography-mass spectrometry
- LIF:
-
Leukemia inhibitory factor
- LIGHT:
-
Tumor necrosis factor superfamily member 14
- L-MSC-S:
-
Limbal mesenchymal stem cell secretome
- LSC-Exo:
-
Lung spheroid cell exosomes
- LSC-sec:
-
Lung spheroid cell secretomes
- MCP-1:
-
Monocyte chemoattractant protein-1
- MDK:
-
Midkine
- MMP:
-
Matrix metalloproteinases
- MSC:
-
Mesenchymal stem cell
- MSC-S:
-
Mesenchymal stem cell–derived secretomes
- MWCO:
-
Molecular weight cut-off
- NGF:
-
Nerve growth factor
- NGF:
-
Nerve growth factor
- NO:
-
Nitric oxide
- NT-:
-
Neurotrophin-
- NT-3:
-
Neurotrophin 3
- PBS:
-
Phosphate buffered saline
- PDGF:
-
Platelet-derived growth factor
- PD-L:
-
Programmed death-ligand
- PEDF:
-
Pigment epithelium-derived factor
- PGE2:
-
Prostaglandin E2
- PGF:
-
Placental growth factor
- PNX-canine model:
-
Pneumonectomy-induced lung injury in a canine model
- PVA:
-
Poly vinyl alcohol
- rBMSC:
-
Rat bone marrow stromal cells
- rOBI:
-
Repetitive ocular blast injury
- RV:
-
Resveratrol
- SDF-1:
-
Stromal cell-derived factor 1
- SD-MSC-S:
-
Skin-derived mesenchymal stem cell secretome
- SOD:
-
Superoxide dismutase
- SPH-MYO:
-
Spheroid-myoblast-conditioned media
- STC1:
-
Stanniocalcin-1
- TCA:
-
Trichloroacetic acid
- TF:
-
Tissue factor
- TGF:
-
Transforming growth factor
- TGF-β1:
-
Transforming growth factor -β1
- TIMP:
-
Metallopeptidase inhibitor
- TNF-α:
-
Tumor necrosis factor alpha
- TSG-6:
-
Tumor necrosis factor stimulated gene 6
- VEGF:
-
Vascularendothelial growth factor
- vWF:
-
vonWillebrand factor
- WJ:
-
Wharton’s jelly
- αMEM:
-
Alpha-minimum essentials medium
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This review is prepared as part of the collaborative work under the Fundamental Research Grant Scheme (FRGS) project funded by the Ministry of Higher Education Malaysia (Project no: DP KPT FRGS/1/2021/SKK06/UM/02/4).
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Conceptualization: NABNA, WSWKZ and NNR. Drafting and revising: NABNA, VV, WSWKZ, NNR, FN and GJT.
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Noor Azlan, N.A.B., Vitus, V., Nor Rashid, N. et al. Human mesenchymal stem cell secretomes: Factors affecting profiling and challenges in clinical application. Cell Tissue Res 395, 227–250 (2024). https://doi.org/10.1007/s00441-023-03857-4
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DOI: https://doi.org/10.1007/s00441-023-03857-4