Analyze Diet
Cytotherapy2010; 12(4); 554-562; doi: 10.3109/14653241003709694

Osteogenic comparison of expanded and uncultured adipose stromal cells.

Abstract: Adipose stromal cells (ASC) are a promising alternative to progenitor cells from other tissue compartments because of their multipotential and capacity to retrieve significantly more progenitor cells. Initial cell samples are heterogeneous, containing a collection of cells that may contribute to tissue repair, but the sample becomes more homogeneous with each passage. Therefore, we hypothesized that the osteogenic potential of culture-expanded ASC would differ from uncultured ASC. Methods: Adipose tissue was collected from a yearling colt, and ASC were isolated and expanded using standard protocols or prepared by a commercial vendor using proprietary technology (proprietary stromal vascular fraction, SVFp). Cells were seeded on collagen sponges and maintained in osteogenic culture conditions for up to 21 days to assess osteogenic potential. The ability of each population to stimulate neovascularization and bone healing was determined upon implanting cell-loaded sponges into a rodent calvarial bone defect. Neovascularization was measured 3 weeks post-implantation, while bone formation was monitored over 12 weeks using in vivo microcomputed tomography (microCT). Results: SVFp exhibited increased intracellular alkaline phosphatase activity compared with cultured ASC but proliferated minimally. Histologic analysis of explanted tissues demonstrated greater vascularization in defects treated with cultured ASC compared with SVFp. We detected increases in bone volume for defects treated with cultured cells while observing similar values for bone mineral density, regardless of cell type. Conclusions: These results suggest that expanded ASC are advantageous for neovascularization and bone healing in this model compared with SVFp, and provide additional evidence of the utility of ASC in bone repair.
Publication Date: 2010-04-08 PubMed ID: 20370353DOI: 10.3109/14653241003709694Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on a study comparing the osteogenic potential of adipose stromal cells (ASC) that have been culture-expanded with that of uncultured ASC, with results denoting the former as more effective in fostering neovascularization and bone healing.

Background & Hypothesis

  • Adipose stromal cells (ASC) present an appealing alternative to progenitor cells drawn from other tissue compartments due to their multipotential nature and ability to yield more progenitor cells.
  • The researchers note that initial ASC samples are heterogeneous, meaning they contain multiple cell types. However, with each cell culture passage, the sample tends towards homogeneity.
  • Due to the shift in composition during the culture expansion, the researchers hypothesize that the osteogenic (bone formation) potential of the cultured ASC will differ from that of the uncultured ASC.

Methodology

  • The study used adipose tissue from a young horse and isolated ASC to be expanded by standard protocols or by a commercial vendor’s proprietary technique, termed proprietary stromal vascular fraction (SVFp).
  • The cultured and uncultured ASC were seeded onto collagen sponges and retained in osteogenic culture conditions for 21 days to measure osteogenic potential.
  • The measure of neovascularization (new blood vessel formation) and bone healing in response to each population was assessed by implanting the cell-infused sponges into a bone defect in a rodent skull.
  • Neovascularization was evaluated 3 weeks post-implantation, and the bone formation process was monitored over 12 weeks, using in vivo microcomputed tomography (microCT).

Results

  • The SVFp cells showed increased intracellular alkaline phosphatase activity compared to cultured ASC but had minimal proliferation.
  • On analysing the explanted tissues, it was ascertained that the areas treated with cultured ASC demonstrated superior vascularization versus the SVFp-treated areas.
  • Increases in bone volume were noted in defects treated with cultured cells, with comparable bone mineral density values observed for both cell types.

Conclusions

  • The study’s findings highlight that cultured ASC proves more beneficial for neovascularization and bone healing in comparison to SVFp, in the examined model.
  • This further reinforces the potential of ASC to contribute to bone repair processes and advancements in related treatments and therapies.

Cite This Article

APA
Cheung WK, Working DM, Galuppo LD, Leach JK. (2010). Osteogenic comparison of expanded and uncultured adipose stromal cells. Cytotherapy, 12(4), 554-562. https://doi.org/10.3109/14653241003709694

Publication

ISSN: 1477-2566
NlmUniqueID: 100895309
Country: England
Language: English
Volume: 12
Issue: 4
Pages: 554-562

Researcher Affiliations

Cheung, Whitney K
  • Department of Biomedical Engineering, School of Veterinary Medicine, University of California, Davis, California 95616, USA.
Working, David M
    Galuppo, Larry D
      Leach, J Kent

        MeSH Terms

        • Animals
        • Calcification, Physiologic
        • Cell Proliferation
        • Cells, Cultured
        • Horses
        • Male
        • Mesenchymal Stem Cell Transplantation
        • Models, Animal
        • Neovascularization, Physiologic
        • Osteogenesis
        • Rats
        • Rats, Nude
        • Skull / blood supply
        • Skull / growth & development
        • Skull / pathology
        • Skull / surgery
        • Skull Fractures / pathology
        • Skull Fractures / therapy
        • Stem Cells / cytology
        • Stem Cells / physiology
        • Stromal Cells / cytology
        • Stromal Cells / physiology
        • Subcutaneous Fat / cytology
        • Transplantation, Heterologous

        Citations

        This article has been cited 27 times.
        1. Hao D, Liu R, Fernandez TG, Pivetti C, Jackson JE, Kulubya ES, Jiang HJ, Ju HY, Liu WL, Panitch A, Lam KS, Leach JK, Farmer DL, Wang A. A bioactive material with dual integrin-targeting ligands regulates specific endogenous cell adhesion and promotes vascularized bone regeneration in adult and fetal bone defects.. Bioact Mater 2023 Feb;20:179-193.
        2. Le Q, Madhu V, Hart JM, Farber CR, Zunder ER, Dighe AS, Cui Q. Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection.. World J Stem Cells 2021 Sep 26;13(9):1248-1277.
          doi: 10.4252/wjsc.v13.i9.1248pubmed: 34630861google scholar: lookup
        3. Negri S, Wang Y, Sono T, Qin Q, Hsu GC, Cherief M, Xu J, Lee S, Tower RJ, Yu V, Piplani A, Meyers CA, Broderick K, Lee M, James AW. Systemic DKK1 neutralization enhances human adipose-derived stem cell mediated bone repair.. Stem Cells Transl Med 2021 Apr;10(4):610-622.
          doi: 10.1002/sctm.20-0293pubmed: 33377628google scholar: lookup
        4. Wang Y, Negri S, Li Z, Xu J, Hsu CY, Peault B, Broderick K, James AW. Anti-DKK1 Enhances the Early Osteogenic Differentiation of Human Adipose-Derived Stem/Stromal Cells.. Stem Cells Dev 2020 Aug 1;29(15):1007-1015.
          doi: 10.1089/scd.2020.0070pubmed: 32460636google scholar: lookup
        5. Hung BP, Gonzalez-Fernandez T, Lin JB, Campbell T, Lee YB, Panitch A, Alsberg E, Leach JK. Multi-peptide presentation and hydrogel mechanics jointly enhance therapeutic duo-potential of entrapped stromal cells.. Biomaterials 2020 Jul;245:119973.
        6. Harvestine JN, Gonzalez-Fernandez T, Sebastian A, Hum NR, Genetos DC, Loots GG, Leach JK. Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates.. Sci Adv 2020 Feb;6(7):eaay2387.
          doi: 10.1126/sciadv.aay2387pubmed: 32095526google scholar: lookup
        7. Ryu NE, Lee SH, Park H. Spheroid Culture System Methods and Applications for Mesenchymal Stem Cells.. Cells 2019 Dec 12;8(12).
          doi: 10.3390/cells8121620pubmed: 31842346google scholar: lookup
        8. Wang Y, Xu J, Chang L, Meyers CA, Zhang L, Broderick K, Lee M, Peault B, James AW. Relative contributions of adipose-resident CD146(+) pericytes and CD34(+) adventitial progenitor cells in bone tissue engineering.. NPJ Regen Med 2019;4:1.
          doi: 10.1038/s41536-018-0063-2pubmed: 30622740google scholar: lookup
        9. Meyers CA, Xu J, Asatrian G, Ding C, Shen J, Broderick K, Ting K, Soo C, Peault B, James AW. WISP-1 drives bone formation at the expense of fat formation in human perivascular stem cells.. Sci Rep 2018 Oct 23;8(1):15618.
          doi: 10.1038/s41598-018-34143-xpubmed: 30353078google scholar: lookup
        10. Meyers CA, Shen J, Lu A, James AW. WNT16 induces proliferation and osteogenic differentiation of human perivascular stem cells.. J Orthop 2018 Sep;15(3):854-857.
          doi: 10.1016/j.jor.2018.08.021pubmed: 30140133google scholar: lookup
        11. Bennett PM, Stewart SK, Dretzke J, Bem D, Penn-Barwell JG. Preclinical therapies to prevent or treat fracture non-union: A systematic review.. PLoS One 2018;13(8):e0201077.
          doi: 10.1371/journal.pone.0201077pubmed: 30067783google scholar: lookup
        12. Roato I, Belisario DC, Compagno M, Verderio L, Sighinolfi A, Mussano F, Genova T, Veneziano F, Pertici G, Perale G, Ferracini R. Adipose-Derived Stromal Vascular Fraction/Xenohybrid Bone Scaffold: An Alternative Source for Bone Regeneration.. Stem Cells Int 2018;2018:4126379.
          doi: 10.1155/2018/4126379pubmed: 29853912google scholar: lookup
        13. James AW, Zhang X, Crisan M, Hardy WR, Liang P, Meyers CA, Lobo S, Lagishetty V, Childers MK, Asatrian G, Ding C, Yen YH, Zou E, Ting K, Peault B, Soo C. Isolation and characterization of canine perivascular stem/stromal cells for bone tissue engineering.. PLoS One 2017;12(5):e0177308.
          doi: 10.1371/journal.pone.0177308pubmed: 28489940google scholar: lookup
        14. Shen J, Chen X, Jia H, Meyers CA, Shrestha S, Asatrian G, Ding C, Tsuei R, Zhang X, Peault B, Ting K, Soo C, James AW. Effects of WNT3A and WNT16 on the Osteogenic and Adipogenic Differentiation of Perivascular Stem/Stromal Cells.. Tissue Eng Part A 2018 Jan;24(1-2):68-80.
          doi: 10.1089/ten.TEA.2016.0387pubmed: 28463594google scholar: lookup
        15. Murphy KC, Hoch AI, Harvestine JN, Zhou D, Leach JK. Mesenchymal Stem Cell Spheroids Retain Osteogenic Phenotype Through α2β1 Signaling.. Stem Cells Transl Med 2016 Sep;5(9):1229-37.
          doi: 10.5966/sctm.2015-0412pubmed: 27365484google scholar: lookup
        16. LaPrade RF, Dragoo JL, Koh JL, Murray IR, Geeslin AG, Chu CR. AAOS Research Symposium Updates and Consensus: Biologic Treatment of Orthopaedic Injuries.. J Am Acad Orthop Surg 2016 Jul;24(7):e62-78.
          doi: 10.5435/JAAOS-D-16-00086pubmed: 27227987google scholar: lookup
        17. Murray IR, Péault B. Q&A: Mesenchymal stem cells - where do they come from and is it important?. BMC Biol 2015 Nov 23;13:99.
          doi: 10.1186/s12915-015-0212-7pubmed: 26596888google scholar: lookup
        18. Yang X, Li CJ, Wan Y, Smith P, Shang G, Cui Q. Antioxidative fullerol promotes osteogenesis of human adipose-derived stem cells.. Int J Nanomedicine 2014;9:4023-31.
          doi: 10.2147/IJN.S66785pubmed: 25187705google scholar: lookup
        19. Binder BY, Sondergaard CS, Nolta JA, Leach JK. Lysophosphatidic acid enhances stromal cell-directed angiogenesis.. PLoS One 2013;8(12):e82134.
          doi: 10.1371/journal.pone.0082134pubmed: 24312635google scholar: lookup
        20. Murray IR, West CC, Hardy WR, James AW, Park TS, Nguyen A, Tawonsawatruk T, Lazzari L, Soo C, Péault B. Natural history of mesenchymal stem cells, from vessel walls to culture vessels.. Cell Mol Life Sci 2014 Apr;71(8):1353-74.
          doi: 10.1007/s00018-013-1462-6pubmed: 24158496google scholar: lookup
        21. Davis HE, Binder BY, Schaecher P, Yakoobinsky DD, Bhat A, Leach JK. Enhancing osteoconductivity of fibrin gels with apatite-coated polymer microspheres.. Tissue Eng Part A 2013 Aug;19(15-16):1773-82.
          doi: 10.1089/ten.TEA.2012.0288pubmed: 23560390google scholar: lookup
        22. Askarinam A, James AW, Zara JN, Goyal R, Corselli M, Pan A, Liang P, Chang L, Rackohn T, Stoker D, Zhang X, Ting K, Péault B, Soo C. Human perivascular stem cells show enhanced osteogenesis and vasculogenesis with Nel-like molecule I protein.. Tissue Eng Part A 2013 Jun;19(11-12):1386-97.
          doi: 10.1089/ten.TEA.2012.0367pubmed: 23406369google scholar: lookup
        23. James AW, Zara JN, Corselli M, Askarinam A, Zhou AM, Hourfar A, Nguyen A, Megerdichian S, Asatrian G, Pang S, Stoker D, Zhang X, Wu B, Ting K, Péault B, Soo C. An abundant perivascular source of stem cells for bone tissue engineering.. Stem Cells Transl Med 2012 Sep;1(9):673-84.
          doi: 10.5966/sctm.2012-0053pubmed: 23197874google scholar: lookup
        24. James AW, Zara JN, Zhang X, Askarinam A, Goyal R, Chiang M, Yuan W, Chang L, Corselli M, Shen J, Pang S, Stoker D, Wu B, Ting K, Péault B, Soo C. Perivascular stem cells: a prospectively purified mesenchymal stem cell population for bone tissue engineering.. Stem Cells Transl Med 2012 Jun;1(6):510-9.
          doi: 10.5966/sctm.2012-0002pubmed: 23197855google scholar: lookup
        25. He J, Decaris ML, Leach JK. Bioceramic-mediated trophic factor secretion by mesenchymal stem cells enhances in vitro endothelial cell persistence and in vivo angiogenesis.. Tissue Eng Part A 2012 Jul;18(13-14):1520-8.
          doi: 10.1089/ten.TEA.2011.0127pubmed: 22546052google scholar: lookup
        26. Zhang X, Péault B, Chen W, Li W, Corselli M, James AW, Lee M, Siu RK, Shen P, Zheng Z, Shen J, Kwak J, Zara JN, Chen F, Zhang H, Yin Z, Wu B, Ting K, Soo C. The Nell-1 growth factor stimulates bone formation by purified human perivascular cells.. Tissue Eng Part A 2011 Oct;17(19-20):2497-509.
          doi: 10.1089/ten.TEA.2010.0705pubmed: 21615216google scholar: lookup
        27. Fite BZ, Decaris M, Sun Y, Sun Y, Lam A, Ho CK, Leach JK, Marcu L. Noninvasive multimodal evaluation of bioengineered cartilage constructs combining time-resolved fluorescence and ultrasound imaging.. Tissue Eng Part C Methods 2011 Apr;17(4):495-504.
          doi: 10.1089/ten.tec.2010.0368pubmed: 21303258google scholar: lookup