Abstract
Background: Transdermal osseointegrated prosthesis have relatively high infection rates leading to implant revision or failure. A principle cause for this complication is the absence of a durable impervious biomechanical seal at the interface of the hard structure (implant) and adjacent soft tissues. This study explores the possibility of recapitulating an analogous cellular musculoskeletal-connective tissue interface, which is present at naturally occurring integumentary tissues where a hard structure exits the skin, such as the nail bed, hoof, and tooth. Methods: Porcine mesenchymal stromal cells (pMSCs) were derived from nine different porcine integumentary and connective tissues: hoof-associated superficial flexor tendon, molar-associated periodontal ligament, Achilles tendon, adipose tissue and skin dermis from the hind limb and abdominal regions, bone marrow and muscle. For all nine pMSCs, the phenotype, multi-lineage differentiation potential and their adhesiveness to clinical grade titanium was characterized. Transcriptomic analysis of 11 common genes encoding cytoskeletal proteins VIM (Vimentin), cell–cell and cell–matrix adhesion genes (Vinculin, Integrin β1, Integrin β2, CD9, CD151), and for ECM genes (Collagen-1a1, Collagen-4a1, Fibronectin, Laminin-α5, Contactin-3) in early passaged cells was performed using qRT-PCR. Results: All tissue-derived pMSCs were characterized as mesenchymal origin by adherence to plastic, expression of cell surface markers including CD29, CD44, CD90, and CD105, and lack of hematopoietic (CD11b) and endothelial (CD31) markers. All pMSCs differentiated into osteoblasts, adipocytes and chondrocytes, albeit at varying degrees, under specific culture conditions. Among the eleven adhesion genes evaluated, the cytoskeletal intermediate filament vimentin was found highly expressed in pMSC isolated from all tissues, followed by genes for the extracellular matrix proteins Fibronectin and Collagen-1a1. Expression of Vimentin was the highest in Achilles tendon, while Fibronectin and Col1agen-1a1 were highest in molar and hoof-associated superficial flexor tendon bone marrow, respectively. Achilles tendon ranked the highest in both multilineage differentiation and adhesion assessments to titanium metal. Conclusions: These findings support further preclinical research of these tissue specific-derived MSCs in vivo in a transdermal osseointegration implant model.
| Original language | English (US) |
|---|---|
| Article number | 604 |
| Journal | Stem Cell Research and Therapy |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2021 |
Bibliographical note
Funding Information:We acknowledge Alisha Rhodes with her help in extracting the porcine molars with the associated ligament tissue; John Mares for continued support in providing access to animals for tissue collection. We thank Safiya Nawabzada for proofreading the manuscript. We also thank Lynda Lopez for technical assistance. Finally, we thank Kateryna Lund and Sintayehu Gebreyohannes from the Biomedical Instrumentation Center at USUHS for their guidance and advice for Flow Cytometry experiments. Authors acknowledge financial support from The U.S. Army Medical Research and Materiel Command (USAMRMC; grant W81XWH-17-2-00590). The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD), the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government.
Funding Information:
Funding was provided by U.S. Army Medical Research and Materiel Command (USAMRMC; Grant W81XWH-17-2-00590).
Publisher Copyright:
© 2021, The Author(s).
Keywords
- Cell adhesion
- Integumentary tissues
- Mesenchymal stromal cells
- Titanium surfaces
- Transdermal osseointegrated implant