Culture and characterization of various porcine integumentary-connective tissue-derived mesenchymal stromal cells to facilitate tissue adhesion to percutaneous metal implants

Stem Cell Research & Therapy

Isha Mutreja¹  Nicholas G. Fischer¹  Conrado Aparicio¹  Cole J. Homer²  Jonathan A. Forsberg³  David T. Danielson³  Thomas A. Davis³  Andrea H. Dragon⁴  Devaveena Dey⁴  Elsa Ronzier⁴  Joan E. Bechtold⁵ 

[1]Department of Restorative Sciences and MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Minneapolis, MN, USA

[2]Department of Restorative Sciences and MDRCBB-Minnesota Dental Research Center for Biomaterials and Biomechanics, University of Minnesota, Minneapolis, MN, USA

[3]Department of Orthopedic Surgery, University of Minnesota, Minneapolis, MN, USA

[4]Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA

[5]Department of Surgery, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, 20814, Bethesda, MD, USA

[6]Henry M Jackson Foundation for Advancement of Military Medicine, Bethesda, USA

[7]Hennepin Healthcare Research Institute, Minneapolis, MN, USA

[8]Department of Orthopedic Surgery, University of Minnesota, Minneapolis, MN, USA

[9]Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA

关键词: Transdermal osseointegrated implant;    Mesenchymal stromal cells;    Integumentary tissues;    Cell adhesion;    Titanium surfaces;   

DOI  :  10.1186/s13287-021-02666-2

来源: Springer

【 摘 要 】

BackgroundTransdermal 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.MethodsPorcine 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.ResultsAll 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.ConclusionsThese findings support further preclinical research of these tissue specific-derived MSCs in vivo in a transdermal osseointegration implant model.

【 授权许可】

CC BY