Emergence of the Stem Cell Secretome in Regenerative Engineering

doi:10.1016/j.tibtech.2020.04.013

Review

. 2020 Dec;38(12):1373-1384.

doi: 10.1016/j.tibtech.2020.04.013. Epub 2020 Jul 1.

Emergence of the Stem Cell Secretome in Regenerative Engineering

Leila Daneshmandi¹, Shiv Shah², Tahereh Jafari³, Maumita Bhattacharjee³, Deandra Momah⁴, Nikoo Saveh-Shemshaki¹, Kevin W-H Lo⁵, Cato T Laurencin⁶

Affiliations

¹ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.
² Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
³ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.
⁴ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.
⁵ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Institute of Materials Science, University of Connecticut, Storrs, CT 06269.
⁶ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA; Institute of Materials Science, University of Connecticut, Storrs, CT 06269; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Medicine, UConn Health, Farmington, CT 06030, USA. Electronic address: Laurencin@uchc.edu.

PMID: 32622558
PMCID: PMC7666064
DOI: 10.1016/j.tibtech.2020.04.013

Review

Emergence of the Stem Cell Secretome in Regenerative Engineering

Leila Daneshmandi et al. Trends Biotechnol. 2020 Dec.

. 2020 Dec;38(12):1373-1384.

doi: 10.1016/j.tibtech.2020.04.013. Epub 2020 Jul 1.

Authors

Leila Daneshmandi¹, Shiv Shah², Tahereh Jafari³, Maumita Bhattacharjee³, Deandra Momah⁴, Nikoo Saveh-Shemshaki¹, Kevin W-H Lo⁵, Cato T Laurencin⁶

Affiliations

¹ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.
² Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA.
³ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.
⁴ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.
⁵ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Institute of Materials Science, University of Connecticut, Storrs, CT 06269.
⁶ Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA; Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA; Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA; Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA; Institute of Materials Science, University of Connecticut, Storrs, CT 06269; Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA; Department of Medicine, UConn Health, Farmington, CT 06030, USA. Electronic address: Laurencin@uchc.edu.

PMID: 32622558
PMCID: PMC7666064
DOI: 10.1016/j.tibtech.2020.04.013

Abstract

The secretome is defined as the set of molecules and biological factors that are secreted by cells into the extracellular space. In the past decade, secretome-based therapies have emerged as a promising approach to overcome the limitations associated with cell-based therapies for tissue and organ regeneration. Considering the growing number of recent publications related to secretome-based therapies, this review takes a step-by-step engineering approach to evaluate the role of the stem cell secretome in regenerative engineering. We discuss the functional benefits of the secretome, the techniques used to engineer the secretome and tailor its therapeutic effects, and the delivery systems and strategies that have been developed to use the secretome for tissue regeneration.

Keywords: conditioned media; regenerative engineering; secretome; stem cell; tissue engineering.

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Figures

**Figure 1.. Schematic Representation of the Secretome and Its Therapeutic Effects.**
Stem cells secrete various soluble factors and extracellular vehicles (including exosomes and microvesicles) that are collectively termed the secretome. These biologically active factors exert therapeutic effects through their proangiogenic, antifibrotic, antiapoptotic, anti-inflammatory, and immunomodulatory properties. Abbreviations: ANG, angiogenin; ANGPT-1, angiopoietin-1; Cyr61, cysteine-rich protein 61; FGF-2, fibroblast growth factor 2; G/M-CSF, granulocyte/macrophage colony stimulating factor; HGF, hepatocyte growth factor; IDO-1, indolamine 2,3-dioxygenase-1; IFN-γ, interferon-γ; IGF-1, insulin-like growth factor-1; IL-1Ra, IL-1 receptor antagonist; IL-6, interleukin-6; MCP-1, monocyte chemoattractant protein-1; MFGE-8, milk fat globule-EGF factor 8; miR-, miRNAs found within the extracellular vesicles; PGE2, prostaglandin E2; SDF-1, stromal-derived factor-1; STC-1, stanniocalcin-1; TGF-β1, transforming growth factor-β1; TIMP-1, tissue inhibitors of metalloproteinase-1; VEGF, vascular endothelial growth factor.

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Ude CC, Schmidt SJ, Laurencin S, Shah S, Esdaille J, Kan HM, Holt BD, Arnold AM, Wolf ME, Nair LS, Sydlik SA, Laurencin CT. Ude CC, et al. Proc Natl Acad Sci U S A. 2023 Nov 7;120(45):e2309156120. doi: 10.1073/pnas.2309156120. Epub 2023 Oct 30. Proc Natl Acad Sci U S A. 2023. PMID: 37903261 Free PMC article.
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References

1. Miller RR and Roubenoff R (2019) Emerging interventions for elderly patients - the promise of regenerative medicine. Clin. Pharmacol. Ther 105, 53–60 - PubMed
1. Laurencin CT and Khan Y (2012) Regenerative engineering. Sci. Transl. Med 4, 160ed9 - PubMed
1. Laurencin CT and Nair LS (2015) Regenerative engineering: approaches to limb regeneration and other grand challenges. Regen. Eng. Transl. Med 1, 1–3 - PMC - PubMed
1. Tang X et al. (2019) Skeletal muscle regenerative engineering. Regen. Eng. Transl. Med 5, 233–251 - PMC - PubMed
1. Lo KW-H et al. (2014) Small-molecule based musculoskeletal regenerative engineering. Trends Biotechnol. 32, 74–81 - PMC - PubMed

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[1] Miller RR and Roubenoff R (2019) Emerging interventions for elderly patients - the promise of regenerative medicine. Clin. Pharmacol. Ther 105, 53–60 - PubMed

[2] Miller RR and Roubenoff R (2019) Emerging interventions for elderly patients - the promise of regenerative medicine. Clin. Pharmacol. Ther 105, 53–60 - PubMed

[3] Laurencin CT and Khan Y (2012) Regenerative engineering. Sci. Transl. Med 4, 160ed9 - PubMed

[4] Laurencin CT and Khan Y (2012) Regenerative engineering. Sci. Transl. Med 4, 160ed9 - PubMed

[5] Laurencin CT and Nair LS (2015) Regenerative engineering: approaches to limb regeneration and other grand challenges. Regen. Eng. Transl. Med 1, 1–3 - PMC - PubMed

[6] Laurencin CT and Nair LS (2015) Regenerative engineering: approaches to limb regeneration and other grand challenges. Regen. Eng. Transl. Med 1, 1–3 - PMC - PubMed

[7] Tang X et al. (2019) Skeletal muscle regenerative engineering. Regen. Eng. Transl. Med 5, 233–251 - PMC - PubMed

[8] Tang X et al. (2019) Skeletal muscle regenerative engineering. Regen. Eng. Transl. Med 5, 233–251 - PMC - PubMed

[9] Lo KW-H et al. (2014) Small-molecule based musculoskeletal regenerative engineering. Trends Biotechnol. 32, 74–81 - PMC - PubMed

[10] Lo KW-H et al. (2014) Small-molecule based musculoskeletal regenerative engineering. Trends Biotechnol. 32, 74–81 - PMC - PubMed

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Emergence of the Stem Cell Secretome in Regenerative Engineering

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Emergence of the Stem Cell Secretome in Regenerative Engineering

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