Translational insights into stem cell preconditioning: From molecular mechanisms to preclinical applications
Open accessAbstract
Cell-based therapy (CBT) is a revolutionary approach for curing a variety of degenerative diseases. Stem cell-based regenerative medicine is a novel strategy for treating tissue damages regarding stem cells unique properties such as differentiation potential, paracrine impacts, and self-renewal ability. However, the current cell-based treatments encounter considerable challenges to be translated into clinical practice, including low cell survival, migration, and differentiation rate of transplanted stem cells. The poor stem cell therapy outcomes mainly originate from the unfavorable condition of damaged tissues for transplanted stem cells. The promising method of preconditioning improves cell resistance against the host environment's stress by imposing certain conditions similar to the harsh microenvironment of the damaged tissues on the transplanted stem cells. Various pharmacological, biological, and physical inducers are able to establish preconditioning. In addition to their known pharmacological effects on tissues and cells, these preconditioning agents improve cell biological aspects such as cell survival, proliferation, differentiation, migration, immunomodulation, paracrine impacts, and angiogenesis. This review focuses on different protocols and inducers of preconditioning along with underlying molecular mechanisms of their effects on stem cell behavior. Moreover, preclinical applications of preconditioned stem cells in various damaged organs such as heart, lung, brain, bone, cartilage, liver, and kidney are discussed with prospects of their translation into the clinic.
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This response phase shifts macrophage polarization toward M2, angiogenesis, stem/progenitor cell migration, and regeneration.
“This response phase has a substantial role in shifting macrophage polarization toward reconstructive phenotype (M2 macrophages), angiogenesis, stem/progenitor cell migration, and collectively, the regeneration process.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [26]
Some cryptic peptides exhibit antimicrobial traits, resulting in low pathogen-related immunogenicity in dECM scaffolds.
“Moreover, some cryptic peptides exhibit antimicrobial traits, resulting in low pathogen-related immunogenicity in decellularized ECM (dECM) scaffolds [25, 26].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [26]
Natural scaffolds undergo a positive host response in which ECM experiences lysis and releases cryptic peptides and growth factors during early degradation.
“Opposite to FBR, natural scaffolds undergo a different positive form of host response, in which ECM experiences lysis and releases some cryptic peptides and growth factors during early degradation.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [26]
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- Authors
- Moeinabadi-Bidgoli, K., Babajani, A., Yazdanpanah, G., Farhadihosseinabadi, B., Jamshidi, E., Bahrami, S., & Niknejad, H.
- Affiliations
- Shahid Beheshti University (IR)
- University of Illinois Chicago (US)
- Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA (AT)
- Corresponding author
- Niknejad, Hassan
- ORCID
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 142
- Pages
- 112026
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W3195914556
- Cited by
- 70
- References
- 191
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 16 · 2023: 20 · 2022: 11
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Shahid Beheshti University of Medical Sciences
- National Institute for Medical Research Development (963951)
- Topics
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- stem cell preconditioning, cell therapy, regenerative medicine, stem cell survival, stem cell migration, immunomodulation, paracrine effects, angiogenesis, tissue regeneration, preclinical applications, clinical translation
- MeSH terms
- Animals, Cell Differentiation, Cell Movement, Cell Survival, Humans, Stem Cells, Stem Cell Transplantation, Regenerative Medicine, Translational Research, Biomedical
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