Tissue Mimicry in Morphology and Composition Promotes Hierarchical Matrix Remodeling of Invading Stem Cells in Osteochondral and Meniscus Scaffolds

2018 ◽  
Vol 30 (28) ◽  
pp. 1706754 ◽  
Author(s):  
Kai Stuckensen ◽  
Andrea Schwab ◽  
Markus Knauer ◽  
Emma Muiños-López ◽  
Franziska Ehlicke ◽  
...  
2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Dolores Javier Sánchez-González ◽  
Enrique Méndez-Bolaina ◽  
Nayeli Isabel Trejo-Bahena

Platelet-derived Growth Factors (GFs) are biologically active peptides that enhance tissue repair mechanisms such as angiogenesis, extracellular matrix remodeling, and cellular effects as stem cells recruitment, chemotaxis, cell proliferation, and differentiation. Platelet-rich plasma (PRP) is used in a variety of clinical applications, based on the premise that higher GF content should promote better healing. Platelet derivatives represent a promising therapeutic modality, offering opportunities for treatment of wounds, ulcers, soft-tissue injuries, and various other applications in cell therapy. PRP can be combined with cell-based therapies such as adipose-derived stem cells, regenerative cell therapy, and transfer factors therapy. This paper describes the biological background of the platelet-derived substances and their potential use in regenerative medicine.


2019 ◽  
Vol 234 (10) ◽  
pp. 18053-18064
Author(s):  
Zhishuai Zhou ◽  
Ying Shen ◽  
Juanjuan Yin ◽  
Feng Xi ◽  
Renjie Xu ◽  
...  

2017 ◽  
Vol 2 (3) ◽  
pp. 2473011417S0004
Author(s):  
Zijun Zhang ◽  
Michael Aynardi ◽  
Talal Zahoor ◽  
Lew Schon

Category: Basic Sciences/Biologics Introduction/Purpose: Achilles tendinopathy and rupture are common and generally can heal without aggressive intervention. When a large defect of Achilles tendon is left by trauma or severe tendinopathy, however, it is a challenge to restore the function of Achilles tendon, because of the size of the tendon and the limitation in Achilles autograft. In contrast, allograft of Achilles tendon does not have restrain of supply. The biology, biomechanics and function of the transplanted Achilles allograft, however, are unknown. Particularly, the revitalization of Achilles allograft is a concern. Mesenchymal stem cells (MSCs) are known for their capability of multi-lineage differentiation and regenerative potentials. Methods: Achilles allografts were harvested from donor rats (approved by Institutional Animal Care and Usage Committee) and kept at -80ºC before transplantation. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of MSCs. MSCs were culture expanded and characterized. On the day of allograft transplantation, adipose tissue derived MSCs were collected and applied onto allografts (1x105 per allograft). Achilles tendon was resected from the left hind limb of the adipose tissue donor rats. Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximately and calcaneus distally. Animal gait was recorded in the week prior to Achilles allograft transplantation (week 0) and every week postoperatively, using a CatWalk system. The transplanted Achilles allografts, with or without MSC incorporation, as well as the normal Achilles tendon in the opposite limbs were harvested at 4 weeks for biomechanical testing and histology. Results: The operated limbs altered gait significantly. By week 4, the recoveries of stand index (speed at which the paw loses contact with ground) and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were not statistically different between the Achilles allograft group and Achilles allograft+MSCs group. Maximum load of failure among Achilles allograft group (27.2±11.5 N), Achilles allograft+MSCs group (27.6±6.4 N) and normal Achilles tendon group (19.9±9.9 N) was not significantly different. On histology, cellularity was generally higher in Achilles allograft+MSCs group than Achilles allograft group (average cellularity grade 2.7±0.5 vs 1.7±0.5). Type III collagen staining was more intense in the Achilles allograft+MSCs group than in the Achilles allograft group. Conclusion: In this pilot study, the allograft incorporated with autologous MSCs demonstrated no significant differences from Achilles allograft alone in maximum failure load and gait analysis. Supplementation of MSCs increased the cellularity and led to more active matrix remodeling in the allograft but these biological improvements did not translate into rat gait and the strength of the implanted allograft. It may be necessary to follow up the animals for an extended period because the remodeling of Achilles allograft takes longer than 4 weeks. In addition, the small size of the rat Achilles allograft might falsely show an accelerated revitalization.


2016 ◽  
Vol 8 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Young Hye Song ◽  
Seung Hee Shon ◽  
Mengrou Shan ◽  
Abraham D Stroock ◽  
Claudia Fischbach

Adipose-derived stem cells (ASCs) are key regulators of extracellular matrix remodeling that modulates neovascularization during tissue regeneration.


2014 ◽  
Vol 289 (12) ◽  
pp. 8402-8412 ◽  
Author(s):  
Marc Mathieu ◽  
Mathieu Iampietro ◽  
Paul Chuchana ◽  
David Guérit ◽  
Farida Djouad ◽  
...  

2020 ◽  
Author(s):  
Ashang Luwang Laiva ◽  
Fergal J. O’Brien ◽  
Michael B. Keogh

Abstract Background: Diabetic foot ulcer is one of the leading causes of leg amputation and mortality in diabetic patients. Autologous stem cell therapy holds some potential to be a solution to this problem, however diabetic stem cells are relatively dysfunctional and restrictive in their wound healing abilities. This study sought to explore if a novel collagen-chondroitin sulfate (coll-CS) scaffold functionalized with polyplex nanoparticles carrying the gene encoding for stromal-derived factor-1 alpha (SDF-1α gene-activated scaffold) can enhance the regenerative functionality of human diabetic adipose-derived stem cells (ADSCs). Methods: Gene-activated scaffolds were first prepared by soak-loading polyethyleneimine nanoparticles carrying the plasmid encoding for SDF-1α gene into a freeze-dried coll-CS scaffold. ADSCs from healthy and diabetic donors were then seeded on the gene-activated scaffold. The response of the ADSCs in the gene-activated scaffold was then compared against those of the healthy ADSCs cultured on the gene-free scaffold over 2 weeks period. Functional response in the ADSCs such as the activation of SDF-1α mediated signaling, production of bioactive factors, pro-angiogenic bioactivity of secreted factors, matrix deposition and remodeling was determined using proteome profiling, Matrigel assay, qRT-PCR and immunofluorescence.Results: Overall, we found that SDF-1α gene-activated scaffold could restore pro-angiogenic regenerative response in the human diabetic ADSCs similar to the healthy ADSCs on the gene-free scaffold. Gene and protein expression analysis revealed that the SDF-1α gene-activated scaffold induced the overexpression of SDF-1α in diabetic ADSCs and engaged the receptor CXCR7, causing downstream signaling of β-arrestin as effectively as the transfected healthy ADSCs. The transfected diabetic ADSCs also effectively stimulated angiogenesis in endothelial cells while undergoing matrix remodeling characterized by reduction in deposition of fibronectin matrix and increase in the expression of basement membrane protein collagen IV. The SDF-1α gene-activated scaffold also induced a controlled pro- healing response in the healthy ADSCs by disabling the signaling of early developmental factors while promoting the expression of tissue remodeling components.Conclusion: We show that the SDF-1α gene-activated scaffold can overcome the deficiencies associated with diabetic ADSCs paving the way for autologous patient stem cell therapies in combination with novel biomaterials to treat diabetic foot ulcers.


Sign in / Sign up

Export Citation Format

Share Document