Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues

Sohnis and Forman Families Center for Stem Cell and Tissue Regeneration Research, Faculty of Medicine, Technion, Haifa, Israel.
Tissue Engineering Part A (Impact Factor: 4.64). 10/2010; 16(10):3119-37. DOI: 10.1089/ten.TEA.2009.0716
Source: PubMed

ABSTRACT The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

  • Source
    • "Characterization of molecular mechanisms responsible for differences in embryonic TPC and adult MSC response to factors may identify pathways that can be controlled to enhance the tenogenic capacity of MSCs. In addition to MSCs, a variety of other stem cells have been explored for tendon tissue engineering, including adipose-derived stem cells, embryonic stem cells, induced pluripotent stem cells, and even adult tendon-derived stem/progenitor cells (Bi et al., 2007; Cohen et al., 2010; James et al., 2011; Xu et al., 2013; Yin et al., 2013; Zhang and Wang, 2010). It is possible that specific stem cell types possess greater tenogenic potential. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tendon is a strong connective tissue that transduces muscle-generated forces into skeletal motion. In fulfilling this role, tendons are subjected to repeated mechanical loading and high stress, which may result in injury. Tissue engineering with stem cells offers the potential to replace injured/damaged tissue with healthy, new living tissue. Critical to tendon tissue engineering is the induction and guidance of stem cells towards the tendon phenotype. Typical strategies have relied on adult tissue homeostatic and healing factors to influence stem cell differentiation, but have yet to achieve tissue regeneration. A novel paradigm is to use embryonic developmental factors as cues to promote tendon regeneration. Embryonic tendon progenitor cell differentiation in vivo is regulated by a combination of mechanical and chemical factors. We propose that these cues will guide stem cells to recapitulate critical aspects of tenogenesis and effectively direct the cells to differentiate and regenerate new tendon. Here, we review recent efforts to identify mechanical and chemical factors of embryonic tendon development to guide stem/progenitor cell differentiation toward new tendon formation, and discuss the role this work may have in the future of tendon tissue engineering.
    Journal of Biomechanics 01/2014; DOI:10.1016/j.jbiomech.2013.12.039 · 2.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The majority of biomass used today is a residue produced either in the primary or secondary processing industries, or as post consumer residues. Many of the industries that process wood or sugar cane are themselves significant consumers of energy in the form of process heat and electricity so that this is a sector with a considerable amount of rankine cycle combined heat and power (CHP) installations. However, many of them underutilize their residues. The advent of export markets for their electricity, due to liberalization and deregulation of electricity supplies, will lead to more efficient CHP installations; the significant energy efficiency measures in the plant operations will result in greater export of electricity. Post consumer residues, as urban wood and landfill gas, already make a significant power contribution in the United States, Europe and Japan. Large scale expansion will require increased harvest residue collection and use in the form of forest thinnings, wood slash, straws and stalks from cereal crops, as well as the development of energy crops. A U.S. supply curve for 2020 will be discussed with its approximately 450 million tonne (Mt) potential, as well as a U.S.A. stretch potential for the middle of the Century of a Gigatonne.
    Power Engineering Society General Meeting, 2004. IEEE; 07/2004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Generation of induced pluripotent stem (iPS) cells using defined factors has been considered a ground-breaking step towards establishing patient-specific pluripotent stem cells for various applications. The isolation of human embryonic stem (ES) cells set the standard that pluripotent stem cells are attainable as potentially immortal cells for regeneration of many types of tissues. Different approaches have been tested to obtain pluripotent stem cells by circumventing the need for embryos. iPS cells appear to be an ideal substitute for ES cells. Since the first demonstration of creating iPS cells in 2006, tremendous efforts have been made into improving iPS cell generation methods and understanding the reprogramming mechanism as well as the nature of iPS cells. To improve iPS cell generation, several approaches have been taken: (1) eliminate the viral vector integration after delivering the defined factors; (2) select different cell types that more effectively give rise to iPS cells; (3) use of chemicals to facilitate reprogramming; (4) use of protein factors to reprogram cells. The iPS cells are also being rigorously characterized in comparison to ES cells. All these efforts are made for the purpose of making iPS cells closer to clinical applications. This article will give an overview of the following areas: (1) mechanisms of iPS cell derivation; (2) characterization of iPS cells; (3) iPS cells for cell-based therapy; and (4) iPS cells for studying disease mechanism. Questions as to what aspects of iPS cells require further understanding before they may be put to clinical use are also discussed.
    10/2010; 2(5):202-217. DOI:10.1016/S1878-3317(10)60033-2
Show more