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Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors.
Arthroscopy 2018; 34(2):581-591A

Abstract

PURPOSE

To evaluate the platelet capture rate of whole blood fibrin clots and the expression, secretion, and retention of the growth factors vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) from fibrin clots and to determine how these levels may be modulated by allogeneic adipose-derived stem cells (ASCs).

METHODS

Whole blood from 10 human volunteers was transferred to a clotting device and the platelet capture rate determined. Two experimental conditions and 1 control were evaluated over 2 weeks in vitro. Clots made from human whole blood without ASCs, clot(-)ASC, were compared with clots with ASCs incorporated, clot(+)ASC, and a control group of synthetic polyethylene glycol gels with ASCs incorporated, control(+)ASCs. All conditions were examined for secretion and retention of VEGF, PDGF, and bFGF via enzyme-linked immunosorbent assay and immunohistochemistry. The analysis of platelet retention for clots made with this device was performed.

RESULTS

Enzyme-linked immunosorbent assay analysis showed significantly higher (P < .001) secretion of VEGF in clot(+)ASC compared with clot(-)ASC or control(+)ASC. In contrast, clot(-)ASC produced soluble PDGF, and the addition of ASCs results in decreased soluble PDGF with concomitant increases in PDGF immunoreactivity of ASCs. Soluble bFGF levels were low in clot(-)ASC, and were found to increase at early time points in clot(+)ASC. Furthermore, bFGF immunoreactivity could be detected in clot(+)ASC, whereas no bFGF immunoreactivity is present in clot(-)ASC or control(+)ASC. Control(+)ASC displayed a spike in bFGF secretion at day 0, which may be due to a stress response elicited by the encapsulation process. Approximately 98% of available platelets in whole blood were concentrated in the clot on formation.

CONCLUSIONS

Fibrin clots made by this method retain high concentrations of platelets, and when incorporated with ASCs show modulated secretion and immunoreactivity of VEGF, PDGF, and bFGF.

CLINICAL RELEVANCE

Whole blood fibrin clots capture platelets and release growth factors, and the addition of ASCs increases VEGF release for up to 2 weeks after clot formation. This suggests that whole blood fibrin clots may be a viable scaffold and delivery vehicle for future stem cell treatments.

Authors+Show Affiliations

Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, U.S.A.. Electronic address: kelsy.siegel@lifesci.ucsb.edu.Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, U.S.A.Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, U.S.A.Center for Stem Cell Biology and Engineering, Neuroscience Research Institute, and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, California, U.S.A.Alta Orthopaedics, Santa Barbara, California, U.S.A.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29100775

Citation

Siegel, Kelsy R., et al. "Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors." Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association, vol. 34, no. 2, 2018, pp. 581-591.
Siegel KR, Clevenger TN, Clegg DO, et al. Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors. Arthroscopy. 2018;34(2):581-591.
Siegel, K. R., Clevenger, T. N., Clegg, D. O., Proctor, D. A., & Proctor, C. S. (2018). Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors. Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 34(2), pp. 581-591. doi:10.1016/j.arthro.2017.08.250.
Siegel KR, et al. Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors. Arthroscopy. 2018;34(2):581-591. PubMed PMID: 29100775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adipose Stem Cells Incorporated in Fibrin Clot Modulate Expression of Growth Factors. AU - Siegel,Kelsy R, AU - Clevenger,Tracy N, AU - Clegg,Dennis O, AU - Proctor,Duncan A, AU - Proctor,Christopher S, PY - 2017/02/09/received PY - 2017/07/30/revised PY - 2017/08/03/accepted PY - 2017/11/5/pubmed PY - 2019/1/22/medline PY - 2017/11/5/entrez SP - 581 EP - 591 JF - Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association JO - Arthroscopy VL - 34 IS - 2 N2 - PURPOSE: To evaluate the platelet capture rate of whole blood fibrin clots and the expression, secretion, and retention of the growth factors vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) from fibrin clots and to determine how these levels may be modulated by allogeneic adipose-derived stem cells (ASCs). METHODS: Whole blood from 10 human volunteers was transferred to a clotting device and the platelet capture rate determined. Two experimental conditions and 1 control were evaluated over 2 weeks in vitro. Clots made from human whole blood without ASCs, clot(-)ASC, were compared with clots with ASCs incorporated, clot(+)ASC, and a control group of synthetic polyethylene glycol gels with ASCs incorporated, control(+)ASCs. All conditions were examined for secretion and retention of VEGF, PDGF, and bFGF via enzyme-linked immunosorbent assay and immunohistochemistry. The analysis of platelet retention for clots made with this device was performed. RESULTS: Enzyme-linked immunosorbent assay analysis showed significantly higher (P < .001) secretion of VEGF in clot(+)ASC compared with clot(-)ASC or control(+)ASC. In contrast, clot(-)ASC produced soluble PDGF, and the addition of ASCs results in decreased soluble PDGF with concomitant increases in PDGF immunoreactivity of ASCs. Soluble bFGF levels were low in clot(-)ASC, and were found to increase at early time points in clot(+)ASC. Furthermore, bFGF immunoreactivity could be detected in clot(+)ASC, whereas no bFGF immunoreactivity is present in clot(-)ASC or control(+)ASC. Control(+)ASC displayed a spike in bFGF secretion at day 0, which may be due to a stress response elicited by the encapsulation process. Approximately 98% of available platelets in whole blood were concentrated in the clot on formation. CONCLUSIONS: Fibrin clots made by this method retain high concentrations of platelets, and when incorporated with ASCs show modulated secretion and immunoreactivity of VEGF, PDGF, and bFGF. CLINICAL RELEVANCE: Whole blood fibrin clots capture platelets and release growth factors, and the addition of ASCs increases VEGF release for up to 2 weeks after clot formation. This suggests that whole blood fibrin clots may be a viable scaffold and delivery vehicle for future stem cell treatments. SN - 1526-3231 UR - https://www.unboundmedicine.com/medline/citation/29100775/Adipose_Stem_Cells_Incorporated_in_Fibrin_Clot_Modulate_Expression_of_Growth_Factors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0749-8063(17)31062-9 DB - PRIME DP - Unbound Medicine ER -