Regenerative Engineering: Studies of the Rotator Cuff and other Musculoskeletal Soft Tissues

MRS Advances ◽  
2016 ◽  
Vol 1 (18) ◽  
pp. 1255-1263 ◽  
Author(s):  
Roshan James ◽  
Paulos Mengsteab ◽  
Cato T. Laurencin
Keyword(s):  
Developmental Biology ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Soft Tissues ◽  
Cell Phenotype ◽  
Cell Lineages ◽  
Regenerative Engineering ◽  
Tissue Systems ◽  
Stem Cell Science ◽  
Advanced Biomaterials

ABSTRACT‘Regenerative Engineering’ is the integration of advanced materials science, stem cell science, physics, developmental biology and clinical translation to regenerate complex tissues and organ systems. Advanced biomaterial and stem cell science converge as mechanisms to guide regeneration and the development of prescribed cell lineages from undifferentiated stem cell populations. Studies in somite development and tissue specification have provided significant insight into pathways of biological regulation responsible for tissue determination, especially morphogen gradients, and paracrine and contact-dependent signaling. The understanding of developmental biology mechanisms are shifting the biomaterial design paradigm by the incorporation of molecules into scaffold design and biomaterial development that are specifically targeted to promote the regeneration of soft tissues. Our understanding allows the selective control of cell sensitivity, and a temporal and spatial arrangement to modulate the wound healing mechanism, and the development of cell phenotype leading to the patterning of distinct and multi-scale tissue systems.Building on the development of mechanically compliant novel biomaterials, the integration of spatiotemporal control of biological, chemical and mechanical cues helps to modulate the stem cell niche and direct the differentiation of stem cell lineages. We have developed advanced biomaterials and biomimetic scaffold designs that can recapitulate the native tissue structure and mechanical compliance of soft musculoskeletal tissues, such as woven scaffold systems for ACL regeneration, non-woven scaffolds for rotator cuff tendon augmentation, and porous elastomers for regeneration of muscle tissue. Studies have clearly demonstrated the modulation of stem cell response to bulk biomaterial properties, such as toughness and elasticity, and scaffold structure, such as nanoscale and microscale dimensions. The integration of biological cues inspired from our understanding of developmental biology, along with chemical, mechanical and electrical stimulation drives our development of novel biomaterials aimed at specifying the stem cell lineage within 3-dimensional (3D) tissue systems. This talk will cover the development of biological cues, advanced biomaterials, and scaffold designs for the regeneration of complex soft musculoskeletal tissue systems such as ligament, tendon, and muscle.

Regenerative engineering: a review of recent advances and future directions

2021 ◽  
Author(s):  
Caldon J Esdaille ◽  
Kenyatta S Washington ◽  
Cato T Laurencin
Keyword(s):  
Developmental Biology ◽  
Stem Cell ◽  
Material Science ◽  
Future Directions ◽  
Advanced Material ◽  
Regenerative Engineering ◽  
The Past ◽  
New Information ◽  
Organ Systems ◽  
Stem Cell Science

Regenerative engineering is defined as the convergence of the disciplines of advanced material science, stem cell science, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems. It is an expansion of tissue engineering, which was first developed as a method of repair and restoration of human tissue. In the past three decades, advances in regenerative engineering have made it possible to treat a variety of clinical challenges by utilizing cutting-edge technology currently available to harness the body’s healing and regenerative abilities. The emergence of new information in developmental biology, stem cell science, advanced material science and nanotechnology have provided promising concepts and approaches to regenerate complex tissues and structures.

Nanotechnology Applications in Stem Cell Science for Regenerative Engineering

2016 ◽  
Vol 16 (9) ◽  
pp. 8953-8965 ◽  
Author(s):  
Varadraj N Vernekar ◽  
Roshan James ◽  
Kevin J Smith ◽  
Cato T Laurencin
Keyword(s):  
Stem Cell ◽  
Regenerative Engineering ◽  
Stem Cell Science

scholarly journals Musculoskeletal Regenerative Engineering: Biomaterials, Structures, and Small Molecules

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Roshan James ◽  
Cato T. Laurencin
Keyword(s):  
Stem Cell ◽  
Materials Science ◽  
Musculoskeletal Tissue ◽  
Tissue Repair And Regeneration ◽  
Musculoskeletal Tissues ◽  
Organ Regeneration ◽  
Organ Systems ◽  
Cell Niche ◽  
Stem Cell Science ◽  
Advanced Biomaterials

Musculoskeletal tissues are critical to the normal functioning of an individual and following damage or degeneration they show extremely limited endogenous regenerative capacity. The future of regenerative medicine is the combination of advanced biomaterials, structures, and cues to re-engineer/guide stem cells to yield the desired organ cells and tissues. Tissue engineering strategies were ideally suited to repair damaged tissues; however, the substitution and regeneration of large tissue volumes and multi-level tissues such as complex organ systems integrated into a single phase require more than optimal combinations of biomaterials and biologics. We highlight bioinspired advancements leading to novel regenerative scaffolds especially for musculoskeletal tissue repair and regeneration. Tissue and organ regeneration relies on the spatial and temporal control of biophysical and biochemical cues, including soluble molecules, cell-cell contacts, cell-extracellular matrix contacts, and physical forces. Strategies that recapitulate the complexity of the local microenvironment of the tissue and the stem cell niche play a crucial role in regulating cell self-renewal and differentiation. Biomaterials and scaffolds based on biomimicry of the native tissue will enable convergence of the advances in materials science, the advances in stem cell science, and our understanding of developmental biology.

Effect of Mechanical Stimulation on the Biomechanics of Stem Cell: Collagen Sponge Constructs for Patellar Tendon Repair

2007 ◽  
Author(s):  
Natalia Juncosa-Melvin ◽  
Jason T. Shearn ◽  
Marc T. Galloway ◽  
Gregory P. Boivin ◽  
Cynthia Gooch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Rotator Cuff ◽  
Mechanical Stimulation ◽  
Soft Tissues ◽  
Tendon Repair ◽  
Collagen Sponge ◽  
Clinical Use ◽  
Attractive Option

Tendons (rotator cuff, Achilles and patellar tendons) are among the most commonly injured soft tissues [1]. Many techniques for repair/reconstruction have been attempted (e.g. sutures, resorbable biomaterials, autografts, and allografts) with varying success. A tissue engineered repair using mesenchymal stem cells (MSCs) is and attractive option [2–4] but the stiffness and strength of currently available constructs are insufficient for clinical use [6].

scholarly journals Engineered stem cell niche matrices for rotator cuff tendon regenerative engineering

PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0174789 ◽  
Author(s):  
M. Sean Peach ◽  
Daisy M. Ramos ◽  
Roshan James ◽  
Nicole L. Morozowich ◽  
Augustus D. Mazzocca ◽  
...  
Keyword(s):  
Stem Cell ◽  
Rotator Cuff ◽  
Stem Cell Niche ◽  
Rotator Cuff Tendon ◽  
Regenerative Engineering ◽  
Cell Niche

scholarly journals Let-7 Represses Carcinogenesis and a Stem Cell Phenotype in the Intestine via Regulation of Hmga2

PLoS Genetics ◽  
2015 ◽  
Vol 11 (8) ◽  
pp. e1005408 ◽  
Author(s):  
Blair B. Madison ◽  
Arjun N. Jeganathan ◽  
Rei Mizuno ◽  
Monte M. Winslow ◽  
Antoni Castells ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Phenotype ◽  
Stem Cell Phenotype

scholarly journals Patterns of Cell Division and the Risk of Cancer

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1527-1532 ◽  
Author(s):  
Steven A Frank ◽  
Yoh Iwasa ◽  
Martin A Nowak
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Basal Layer ◽  
Mutation Rates ◽  
Tissue Architecture ◽  
Cell Lineages ◽  
Cell Mutation ◽  
Long Stem ◽  
Risk Of Cancer ◽  
Transit Cell

Abstract Epidermal and intestinal tissues divide throughout life to replace lost surface cells. These renewing tissues have long-lived basal stem cell lineages that divide many times, each division producing one stem cell and one transit cell. The transit cell divides a limited number of times, producing cells that move up from the basal layer and eventually slough off from the surface. If mutation rates are the same in stem and transit divisions, we show that minimal cancer risk is obtained by using the fewest possible stem divisions subject to the constraints imposed by the need to renew the tissue. In this case, stem cells are a necessary risk imposed by the constraints of tissue architecture. Cairns suggested that stem cells may have lower mutation rates than transit cells do. We develop a mathematical model to study the consequences of different stem and transit mutation rates. Our model shows that stem cell mutation rates two or three orders of magnitude less than transit mutation rates may favor relatively more stem divisions and fewer transit divisions, perhaps explaining how renewing tissues allocate cell divisions between long stem and short transit lineages.

scholarly journals GSK3β, a Master Kinase in the Regulation of Adult Stem Cell Behavior

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 225
Author(s):  
Claire Racaud-Sultan ◽  
Nathalie Vergnolle
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Glycogen Synthase ◽  
Inflammatory Diseases ◽  
Adult Stem Cell ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Epithelial Regeneration ◽  
Cell Functions

In adult stem cells, Glycogen Synthase Kinase 3β (GSK3β) is at the crossroad of signaling pathways controlling survival, proliferation, adhesion and differentiation. The microenvironment plays a key role in the regulation of these cell functions and we have demonstrated that the GSK3β activity is strongly dependent on the engagement of integrins and protease-activated receptors (PARs). Downstream of the integrin α5β1 or PAR2 activation, a molecular complex is organized around the scaffolding proteins RACK1 and β-arrestin-2 respectively, containing the phosphatase PP2A responsible for GSK3β activation. As a consequence, a quiescent stem cell phenotype is established with high capacities to face apoptotic and metabolic stresses. A protective role of GSK3β has been found for hematopoietic and intestinal stem cells. Latters survived to de-adhesion through PAR2 activation, whereas formers were protected from cytotoxicity through α5β1 engagement. However, a prolonged activation of GSK3β promoted a defect in epithelial regeneration and a resistance to chemotherapy of leukemic cells, paving the way to chronic inflammatory diseases and to cancer resurgence, respectively. In both cases, a sexual dimorphism was measured in GSK3β-dependent cellular functions. GSK3β activity is a key marker for inflammatory and cancer diseases allowing adjusted therapy to sex, age and metabolic status of patients.

scholarly journals The Epithelial–Mesenchymal Transcription Factor SNAI1 Represses Transcription of the Tumor Suppressor miRNA let-7 in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1469
Author(s):  
Hanmin Wang ◽  
Evgeny Chirshev ◽  
Nozomi Hojo ◽  
Tise Suzuki ◽  
Antonella Bertucci ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Stem Cell ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Burden ◽  
Cell Phenotype ◽  
Mesenchymal Transition ◽  
Carcinoma Cell Lines ◽  
Future Work

We aimed to determine the mechanism of epithelial–mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linked let-7 repression and acquisition of stemness with the EMT factor, SNAI1. The mechanisms for the loss of let-7 in cancer cells are incompletely understood. In four carcinoma cell lines from breast cancer, pancreatic cancer, and ovarian cancer and in ovarian cancer patient-derived cells, we analyzed stem cell phenotype and tumor growth via mRNA, miRNA, and protein expression, spheroid formation, and growth in patient-derived xenografts. We show that treatment with EMT-promoting growth factors or SNAI1 overexpression increased stemness and reduced let-7 expression, while SNAI1 knockdown reduced stemness and restored let-7 expression. Rescue experiments demonstrate that the pro-stemness effects of SNAI1 are mediated via let-7. In vivo, nanoparticle-delivered siRNA successfully knocked down SNAI1 in orthotopic patient-derived xenografts, accompanied by reduced stemness and increased let-7 expression, and reduced tumor burden. Chromatin immunoprecipitation demonstrated that SNAI1 binds the promoters of various let-7 family members, and luciferase assays revealed that SNAI1 represses let-7 transcription. In conclusion, the SNAI1/let-7 axis is an important component of stemness pathways in cancer cells, and this study provides a rationale for future work examining this axis as a potential target for cancer stem cell-specific therapies.

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