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Michael J Mienaltowski - One of the best experts on this subject based on the ideXlab platform.

  • Adding exogenous biglycan or decorin improves tendon formation for equine Peritenon and tendon proper cells in vitro
    BMC Musculoskeletal Disorders, 2020
    Co-Authors: Monica Y. Pechanec, Tannah N. Boyd, Keith Baar, Michael J Mienaltowski
    Abstract:

    Background Tendon injuries amount to one of the leading causes of career-ending injuries in horses due to the inability for tendon to completely repair and the high reinjury potential. As a result, novel therapeutics are necessary to improve repair with the goal of decreasing leg lameness and potential reinjury. Small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules responsible for collagen organization and maturation, may be one such therapeutic to improve tendon repair. Before SLRP supplementation can occur in vivo, proper evaluation of the effect of these molecules in vitro needs to be assessed. The objective of this study was to evaluate the effectiveness of purified bovine biglycan or decorin on tendon proper and Peritenon cell populations in three-dimensional tendon constructs. Methods Equine tendon proper or Peritenon cell seeded fibrin three-dimensional constructs were supplemented with biglycan or decorin at two concentrations (5 nM or 25 nM). The functionality and ultrastructural morphology of the constructs were assessed using biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression by real time – quantitative polymerase chain reaction (RT-qPCR). Results SLRP supplementation affected both tendon proper and Peritenon cells-seeded constructs. With additional SLRPs, material and tensile properties of constructs strengthened, though ultrastructural analyses indicated production of similar-sized or smaller fibrils. Overall expression of tendon markers was bolstered more in Peritenon cells supplemented with either SLRP, while supplementation of SLRPs to TP cell-derived constructs demonstrated fewer changes in tendon and extracellular matrix markers. Moreover, relative to non-supplemented tendon proper cell-seeded constructs, SLRP supplementation of the Peritenon cells showed increases in mechanical strength, material properties, and collagen content. Conclusions The SLRP-supplemented Peritenon cells produced constructs with greater mechanical and material properties than tendon proper seeded constructs, as well as increased expression of matrix assembly molecules. These findings provide evidence that SLRPs should be further investigated for their potential to improve tendon formation in engineered grafts or post-injury.

  • adding exogenous biglycan or decorin improves tendon formation for equine Peritenon and tendon proper cells in vitro
    BMC Musculoskeletal Disorders, 2020
    Co-Authors: Monica Y. Pechanec, Tannah N. Boyd, Keith Baar, Michael J Mienaltowski
    Abstract:

    Author(s): Pechanec, Monica Y; Boyd, Tannah N; Baar, Keith; Mienaltowski, Michael J | Abstract: BackgroundTendon injuries amount to one of the leading causes of career-ending injuries in horses due to the inability for tendon to completely repair and the high reinjury potential. As a result, novel therapeutics are necessary to improve repair with the goal of decreasing leg lameness and potential reinjury. Small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules responsible for collagen organization and maturation, may be one such therapeutic to improve tendon repair. Before SLRP supplementation can occur in vivo, proper evaluation of the effect of these molecules in vitro needs to be assessed. The objective of this study was to evaluate the effectiveness of purified bovine biglycan or decorin on tendon proper and Peritenon cell populations in three-dimensional tendon constructs.MethodsEquine tendon proper or Peritenon cell seeded fibrin three-dimensional constructs were supplemented with biglycan or decorin at two concentrations (5 nM or 25 nM). The functionality and ultrastructural morphology of the constructs were assessed using biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression by real time - quantitative polymerase chain reaction (RT-qPCR).ResultsSLRP supplementation affected both tendon proper and Peritenon cells-seeded constructs. With additional SLRPs, material and tensile properties of constructs strengthened, though ultrastructural analyses indicated production of similar-sized or smaller fibrils. Overall expression of tendon markers was bolstered more in Peritenon cells supplemented with either SLRP, while supplementation of SLRPs to TP cell-derived constructs demonstrated fewer changes in tendon and extracellular matrix markers. Moreover, relative to non-supplemented tendon proper cell-seeded constructs, SLRP supplementation of the Peritenon cells showed increases in mechanical strength, material properties, and collagen content.ConclusionsThe SLRP-supplemented Peritenon cells produced constructs with greater mechanical and material properties than tendon proper seeded constructs, as well as increased expression of matrix assembly molecules. These findings provide evidence that SLRPs should be further investigated for their potential to improve tendon formation in engineered grafts or post-injury.

  • transcriptome profiles of isolated murine achilles tendon proper and Peritenon derived progenitor cells
    Journal of Orthopaedic Research, 2019
    Co-Authors: Michael J Mienaltowski, Monica Y. Pechanec, A Canovas, Valerie A Fates, Angela R Hampton, Alma Islastrejo, Juan F Medrano
    Abstract:

    Progenitor cells of the tendon proper and Peritenon have unique properties that could impact their utilization in tendon repair strategies. While a few markers have been found to aid in distinguishing progenitors cells from each region, there is great value in identifying more markers. In this study, we hypothesized that RNAseq could be used to improve our understanding of those markers that define these cell types. Transcriptome profiles were generated for pools of mouse Achilles tendon progenitor cells from both regions and catalogues of potential markers were generated. Moreover, common (e.g., glycoprotein, signaling, and proteinaceous extracellular matrix) and unique (e.g., cartilage development versus angiogenesis and muscle contraction) biological processes and molecular functions were described for progenitors from each region. Real-time quantitative PCR of a subset of genes was used to gain insight into the heterogeneity amongst individual progenitor colonies from each region. Markers like Scx, Mkx, Thbs4, and Wnt10a were consistently able to distinguish tendon proper progenitors from Peritenon progenitors; expression variability for other genes suggested greater cell type complexity for potential Peritenon progenitor markers. This is the first effort to define Achilles tendon progenitor markers by region. Further efforts to investigate the value of these cataloged markers are required by screening more individual colonies of progenitors for more markers. Clinical Significance: Findings from this study advance efforts in the discernment of cell type specific markers for tendon proper and Peritenon progenitor cells; insight into marker sets could improve tracking and sorting strategies for these cells for future therapeutic strategies. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1409-1418, 2019.

  • Tendon proper- and Peritenon-derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials. Methods Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, Peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types. Results The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the Peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to Peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in Peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that Peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors. Conclusions Data demonstrate that, relative to Peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by Peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies.

  • tendon proper and Peritenon derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.

David E Birk - One of the best experts on this subject based on the ideXlab platform.

  • Tendon proper- and Peritenon-derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials. Methods Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, Peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types. Results The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the Peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to Peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in Peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that Peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors. Conclusions Data demonstrate that, relative to Peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by Peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies.

  • tendon proper and Peritenon derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.

Jess G. Snedeker - One of the best experts on this subject based on the ideXlab platform.

  • Differences between the Cell Populations from the Peritenon and the Tendon Core with Regard to Their Potential Implication in Tendon Repair
    2016
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, Rene ́ P. Van Weeren, Jess G. Snedeker
    Abstract:

    The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the Peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and Peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in Peritenon cells. Cells from the Peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the Peritenon have substantia

  • differences between the cell populations from the Peritenon and the tendon core with regard to their potential implication in tendon repair
    PLOS ONE, 2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the Peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and Peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in Peritenon cells. Cells from the Peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the Peritenon have substantial potential to influence tendon-healing outcome, warranting further scrutiny of their role.

  • Clonogenicity of the two cell populations.
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    Representative wells with colonies from the tendon core population (A) and from the Peritenon population (B) were evaluated (n = 14; the cells were from seven different horses; scale bar  = 0.5 cm). The cells isolated from the tendon core demonstrated 2.6 times more colonies compared to the Peritenon cell population (C; p = 0.02). The colonies were 2.5 times larger in the Peritenon cell population than in the cells isolated from the tendon core (D; p = 0.018).

  • Migration and replication rate.
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    (A) Average migration speed of the cell populations from the core of the tendon and from the Peritenon, obtained with a scratch assay monitored over 8 h. The Peritenon cell population was 1.2 times faster than the tendon core population (p  = 0.04). The cells were from twelve different horses. (B) Replication rate: Starting with equivalent numbers of cells, we calculated the number of cells after 7 days in culture in expansion medium. There were 1.33 times more cells in the flasks containing cells isolated from the Peritenon compared to the flasks containing cells isolated from the tendon core (p = 0.026). The cells were from four different horses.

  • Comparison of the propensity to differentiate into myofibroblasts of the cell populations from the Peritenon and from the core of the tendon and the effects of ligands on the differentiation propensity of cells isolated from the Peritenon and cells i
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    (A–C) Expression of myofibroblast marker α-SMA was assessed by Western blotting together with loading control vimentin. (B–D) Band signal strength in Western blots was analyzed by optical densitometry and related to loading control vimentin. (A–B)Following addition of TGF-β1, the level of α-SMA was 2.4 times increased in the cell population from the tendon core and 3.6 times increased in the cell population from the Peritenon. The cell population from the Peritenon showed a 1.2-fold increased expression of α-SMA compared to the cell population from the tendon core when cultured with TGF-β1. (C–D) The cell population from the Peritenon showed a 1.7-fold increase of α-SMA expression on 100 kPa PDMS dishes coated with collagen compared to the cell population of the tendon core and a 4-fold increase of α-SMA expression on same dishes coated with fibronectin (for both experiments, the cells were extracted from three different horses).

Jennifer A. Cadby - One of the best experts on this subject based on the ideXlab platform.

  • Differences between the Cell Populations from the Peritenon and the Tendon Core with Regard to Their Potential Implication in Tendon Repair
    2016
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, Rene ́ P. Van Weeren, Jess G. Snedeker
    Abstract:

    The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the Peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and Peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in Peritenon cells. Cells from the Peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the Peritenon have substantia

  • differences between the cell populations from the Peritenon and the tendon core with regard to their potential implication in tendon repair
    PLOS ONE, 2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    The role of intrinsic and extrinsic healing in injured tendons is still debated. In this study, we characterized cell plasticity, proliferative capacity, and migration characteristics as proxy measures of healing potential in cells derived from the Peritenon (extrinsic healing) and compared these to cells from the tendon core (intrinsic healing). Both cell populations were extracted from horse superficial digital flexor tendon and characterized for tenogenic and matrix remodeling markers as well as for rates of migration and replication. Furthermore, colony-forming unit assays, multipotency assays, and real-time quantitative polymerase chain reaction analyses of markers of osteogenic and adipogenic differentiation after culture in induction media were performed. Finally, cellular capacity for differentiation towards a myofibroblastic phenotype was assessed. Our results demonstrate that both tendon- and Peritenon-derived cell populations are capable of adipogenic and osteogenic differentiation, with higher expression of progenitor cell markers in Peritenon cells. Cells from the Peritenon also migrated faster, replicate more quickly, and show higher differentiation potential toward a myofibroblastic phenotype when compared to cells from the tendon core. Based on these data, we suggest that cells from the Peritenon have substantial potential to influence tendon-healing outcome, warranting further scrutiny of their role.

  • Clonogenicity of the two cell populations.
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    Representative wells with colonies from the tendon core population (A) and from the Peritenon population (B) were evaluated (n = 14; the cells were from seven different horses; scale bar  = 0.5 cm). The cells isolated from the tendon core demonstrated 2.6 times more colonies compared to the Peritenon cell population (C; p = 0.02). The colonies were 2.5 times larger in the Peritenon cell population than in the cells isolated from the tendon core (D; p = 0.018).

  • Migration and replication rate.
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    (A) Average migration speed of the cell populations from the core of the tendon and from the Peritenon, obtained with a scratch assay monitored over 8 h. The Peritenon cell population was 1.2 times faster than the tendon core population (p  = 0.04). The cells were from twelve different horses. (B) Replication rate: Starting with equivalent numbers of cells, we calculated the number of cells after 7 days in culture in expansion medium. There were 1.33 times more cells in the flasks containing cells isolated from the Peritenon compared to the flasks containing cells isolated from the tendon core (p = 0.026). The cells were from four different horses.

  • Comparison of the propensity to differentiate into myofibroblasts of the cell populations from the Peritenon and from the core of the tendon and the effects of ligands on the differentiation propensity of cells isolated from the Peritenon and cells i
    2014
    Co-Authors: Jennifer A. Cadby, Evelyne Buehler, Charles Godbout, René P. Van Weeren, Jess G. Snedeker
    Abstract:

    (A–C) Expression of myofibroblast marker α-SMA was assessed by Western blotting together with loading control vimentin. (B–D) Band signal strength in Western blots was analyzed by optical densitometry and related to loading control vimentin. (A–B)Following addition of TGF-β1, the level of α-SMA was 2.4 times increased in the cell population from the tendon core and 3.6 times increased in the cell population from the Peritenon. The cell population from the Peritenon showed a 1.2-fold increased expression of α-SMA compared to the cell population from the tendon core when cultured with TGF-β1. (C–D) The cell population from the Peritenon showed a 1.7-fold increase of α-SMA expression on 100 kPa PDMS dishes coated with collagen compared to the cell population of the tendon core and a 4-fold increase of α-SMA expression on same dishes coated with fibronectin (for both experiments, the cells were extracted from three different horses).

Sheila M Adams - One of the best experts on this subject based on the ideXlab platform.

  • Tendon proper- and Peritenon-derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials. Methods Isolated progenitors were seeded within fibrinogen/thrombin gel-based constructs with or without supplementation with recombinant growth/differentiation factor-5 (GDF5). Early and late in culture, gene expression of differentiation markers and matrix assembly genes was analyzed. Tendon construct ultrastructure was also compared after 45 days. Moreover, conditioned media from tendon proper-derived progenitors, Peritenon-derived progenitors, or tenocytes was applied to each of the three cell types to determine paracrine stimulatory effects of the factors secreted from each of the respective cell types. Results The cell orientation, extracellular domain and fibril organization of constructs were comparable to embryonic tendon. The tendon proper-derived progenitors produced a more tendon-like construct than the Peritenon-derived progenitors. Seeded tendon proper-derived progenitors expressed greater levels of tenogenic markers and matrix assembly genes, relative to Peritenon-derived progenitors. However, GDF5 supplementation improved expression of matrix assembly genes in Peritenon progenitors and structurally led to increased mean fibril diameters. It also was found that Peritenon-derived progenitors secrete factor(s) stimulatory to tenocytes and tendon proper progenitors. Conclusions Data demonstrate that, relative to Peritenon-derived progenitors, tendon proper progenitors have greater potential for forming functional tendon-like tissue. Furthermore, factors secreted by Peritenon-derived progenitors suggest a trophic role for this cell type as well. Thus, these findings highlight the synergistic potential of including these progenitor populations in restorative tendon engineering strategies.

  • tendon proper and Peritenon derived progenitor cells have unique tenogenic properties
    Stem Cell Research & Therapy, 2014
    Co-Authors: Michael J Mienaltowski, Sheila M Adams, David E Birk
    Abstract:

    Introduction Multipotent progenitor populations exist within the tendon proper and Peritenon of the Achilles tendon. Progenitor populations derived from the tendon proper and Peritenon are enriched with distinct cell types that are distinguished by expression of markers of tendon and vascular or pericyte origins, respectively. The objective of this study was to discern the unique tenogenic properties of tendon proper- and Peritenon-derived progenitors within an in vitro model. We hypothesized that progenitors from each region contribute differently to tendon formation; thus, when incorporated into a regenerative model, progenitors from each region will respond uniquely. Moreover, we hypothesized that cell populations like progenitors were capable of stimulating tenogenic differentiation, so we generated conditioned media from these cell types to analyze their stimulatory potentials.