Human Developmental Chondrogenesis as a Basis for Engineering Chondrocytes from Pluripotent Stem Cells

Joint injury and osteoarthritis affect millions of people worldwide, but attempts to generate articular cartilage using adult stem/progenitor cells have been unsuccessful. We hypothesized that recapitulation of the human developmental chondrogenic program using pluripotent stem cells (PSCs) may represent a superior approach for cartilage restoration. Using laser-capture microdissection followed by microarray analysis, we first defined a surface phenotype (CD166(low/neg)CD146(low/neg)CD73(+)CD44(low)BMPR1B(+)) distinguishing the earliest cartilage committed cells (prechondrocytes) at 5-6 weeks of development. Functional studies confirmed these cells are chondrocyte progenitors. From 12 weeks, only the superficial layers of articular cartilage were enriched in cells with this progenitor phenotype. Isolation of cells with a similar immunophenotype from differentiating human PSCs revealed a population of CD166(low/neg)BMPR1B(+) putative cartilage-committed progenitors. Taken as a whole, these data define a developmental approach for the generation of highly purified functional human chondrocytes from PSCs that could enable substantial progress in cartilage tissue engineering.Fil: Wu, Ling. University of California at Los Angeles; Estados UnidosFil: Bluguermann, Carolina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California at Los Angeles; Estados UnidosFil: Kyupelyan, Levon. University of California at Los Angeles; Estados UnidosFil: Latour, Brooke. University of California at Los Angeles; Estados UnidosFil: Gonzalez, Stephanie. University of California at Los Angeles; Estados UnidosFil: Shah, Saumya. University of California at Los Angeles; Estados UnidosFil: Galic, Zoran. University of California at Los Angeles; Estados UnidosFil: Ge, Sundi. University of California at Los Angeles; Estados UnidosFil: Zhu, Yuhua. University of California at Los Angeles; Estados UnidosFil: Petrigliano, Frank A.. University of California at Los Angeles; Estados UnidosFil: Nsair, Ali. University of California at Los Angeles; Estados UnidosFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Li, Xinmin. University of California at Los Angeles; Estados UnidosFil: Lyons, Karen M.. University of California at Los Angeles; Estados UnidosFil: Crooks, Gay M.. University of California at Los Angeles; Estados UnidosFil: McAllister, David R.. University of California at Los Angeles; Estados UnidosFil: Van Handel, Ben. Novogenix Laboratories; Estados UnidosFil: Adams, John S.. University of California at Los Angeles; Estados UnidosFil: Evseenko, Denis. University of California at Los Angeles; Estados Unido

Implant Engineering in the Age of Biologics.

Implants and their technological advances have been a critical component of musculoskeletal care for almost a century. Modern implants are designed to enhance bone ingrowth, promote soft-tissue healing, and prevent infection. Porous metals and short-stem fixation devices have rendered previously unreconstructable bony deficits reconstructable. Stem cells, growth factors, and novel biocompatible compounds have been designed to promote and enhance soft tissue attachment to implants. Antimicrobial modifications have been engineered onto implants to deter bacterial attachment, and innovative surface modifications and eluting technologies may be in our near future. Yet, given the enormous economic pressures in orthopaedics, marketing claims of innovation often exceed scientific accomplishment. Vigilance is thus required in distinguishing transformational discovery from unsubstantiated claims

Novel aspects of parenchymal–mesenchymal interactions: from cell types to molecules and beyond

Mesenchymal stem or stromal cells (MSCs) were initially isolated from the bone marrow and received their name on the basis of their ability to differentiate into multiple lineages such as bone, cartilage, fat and muscle. However, more recent studies suggest that MSCs residing in perivascular compartments of the small and large blood vessels play a regulatory function supporting physiologic and pathologic responses of parenchymal cells, which define the functional representation of an organ or tissue. MSCs secrete or express factors that reach neighbouring parenchymal cells via either a paracrine effect or a direct cell-to-cell interaction promoting functional activity, survival and proliferation of the parenchymal cells. Previous concept of ´epithelial-stromal´ interactions can now be widened. Given that MSC can also support hematopoietic, neuronal and other non-epithelial parenchymal lineages, terms ´parenchymal-stromal´ or ´parenchymal-mesenchymal´ interactions may better describe the supportive or ´trophic´ functions of MSC. Importantly, in many cases, MSCs specifically provide supportive microenvironment for the most primitive stem or progenitor populations and therefore can play a role as ´stem/progenitor niche´ forming cells. So far, regulatory roles of MSCs have been reported in many tissues. In this review article, we summarize the latest studies that focused on the supportive function of MSC. This thread of research leads to a new perspective on the interactions between parenchymal and mesenchymal cells and justifies a principally novel approach for regenerative medicine based on co-application of MSC and parenchymal cell for the most efficient tissue repair.Fil: Bluguermann, Carolina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. University of California at Los Angeles; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wu, Ling. University of California at Los Angeles; Estados UnidosFil: Petrigliano, Frank. University of California at Los Angeles; Estados UnidosFil: McAllister, David. University of California at Los Angeles; Estados UnidosFil: Miriuka, Santiago Gabriel. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Laboratorio de Biología del Desarrollo Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Evseenko, Denis A.. University of California at Los Angeles; Estados Unido

In Vivo Evaluation of Electrospun Polycaprolactone Graft for Anterior Cruciate Ligament Engineering

The anterior cruciate ligament (ACL) is critical for the structural stability of the knee and its injury often requires surgical intervention. Because current reconstruction methods using autograft or allograft tissue suffer from donor-site morbidity and limited supply, there has been emerging interest in the use of bioengineered materials as a platform for ligament reconstruction. Here, we report the use of electrospun polycaprolactone (PCL) scaffolds as a candidate platform for ACL reconstruction in an in vivo rodent model. Electrospun PCL was fabricated and laser cut to facilitate induction of cells and collagen deposition and used to reconstruct the rat ACL. Histological analysis at 2, 6, and 12 weeks postimplantation revealed biological integration, minimal immune response, and the gradual infiltration of collagen in both the bone tunnel and intra-articular regions of the scaffold. Biomechanical testing demonstrated that the PCL graft failure load and stiffness at 12 weeks postimplantation (13.27±4.20N, 15.98±5.03 N/mm) increased compared to time zero testing (3.95±0.33N, 1.95±0.35 N/mm). Taken together, these results suggest that electrospun PCL serves as a biocompatible graft for ACL reconstruction with the capacity to facilitate collagen deposition