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Informing Stem Cell-Based Tendon Tissue Engineering Approaches with Embryonic Tendon Development

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Metabolic Influences on Risk for Tendon Disorders

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 920))

Abstract

Adult tendons fail to regenerate normal tissue after injury, and instead form dysfunctional scar tissue with abnormal mechanical properties. Surgical repair with grafts is the current standard to treat injuries, but faces significant limitations including pain and high rates of re-injury. To address this, we aim to regenerate new, normal tendons to replace dysfunctional tendons. A common approach to tendon tissue engineering is to design scaffolds and bioreactors based on adult tendon properties that can direct adult stem cell tenogenesis. Despite significant progress, advances have been limited due, in part, to a need for markers and potent induction cues. Our goal is to develop novel tendon tissue engineering approaches informed by embryonic tendon development. We are characterizing structure–property relationships of embryonic tendon to identify design parameters for three-dimensional scaffolds and bioreactor mechanical loading systems to direct adult stem cell tenogenesis. We will review studies in which we quantified changes in the mechanical and biochemical properties of tendon during embryonic development and elucidated specific mechanisms of functional property elaboration. We then examined the effects of these mechanical and biochemical factors on embryonic tendon cell behavior. Using custom-designed bioreactors, we also examined the effects of dynamic mechanical loading and growth factor treatment on embryonic tendon cells. Our findings have established cues to induce tenogenesis as well as metrics to evaluate differentiation. We finish by discussing how we have evaluated the tenogenic differentiation potential of adult stem cells by comparing their responses to that of embryonic tendon cells in these culture systems.

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Abbreviations

3D:

Three-dimensional

BAPN:

Beta-aminopropionitrile

Col I:

Collagen I

Col III:

Collagen III

Col XII:

Collagen XII

DAPI:

4′,6-Diamidino-2-Phenylindole, Dihydrochloride

DMAB:

p-Dimethylaminobenzaldehyde

DNA:

Deoxyribonucleic acid

E:

Embryonic day

ECM:

Extracellular matrix

Egr-1:

Early growth response-1

FGF4:

Fibroblast growth factor 4

FGF8:

Fibroblast growth factor 8

FV-AFM:

Force volume-atomic force microscopy

GFP:

Green fluorescent protein

HH:

Hamilton and Hamburger

HP:

Hydroxylysyl pyridinoline

LP:

Lysyl pyridinoline

LC-MS/MS:

Liquid chromatography tandem-mass spectrometry

LOX:

Lysyl oxidase

Mkx:

Mohawk

MSC:

Mesenchymal stem cell

P:

Postnatal day

PDGF:

Platelet-derived growth factor

Scx:

Scleraxis

SHG:

Second Harmonic Generation

TGFβ1 :

Transforming growth factor beta 1

TGFβ2 :

Transforming growth factor beta 2

Tnmd:

Tenomodulin

TPC:

Tendon progenitor cell

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Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, University of Rochester, 215 Robert B. Goergen Hall, 270168, Rochester, NY, 14627-0168, USA

    William Okech & Catherine K. Kuo

  2. Department of Orthopaedics, University of Rochester, 215 Robert B. Goergen Hall, 270168, Rochester, NY, 14627-0168, USA

    Catherine K. Kuo

  3. Center for Musculoskeletal Research, University of Rochester, 215 Robert B. Goergen Hall, 270168, Rochester, NY, 14627-0168, USA

    Catherine K. Kuo

Authors
  1. William Okech
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  2. Catherine K. Kuo
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Corresponding author

Correspondence to Catherine K. Kuo .

Editor information

Editors and Affiliations

  1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Paul W. Ackermann

  2. McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada

    David A. Hart

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Okech, W., Kuo, C.K. (2016). Informing Stem Cell-Based Tendon Tissue Engineering Approaches with Embryonic Tendon Development. In: Ackermann, P., Hart, D. (eds) Metabolic Influences on Risk for Tendon Disorders. Advances in Experimental Medicine and Biology, vol 920. Springer, Cham. https://doi.org/10.1007/978-3-319-33943-6_6

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