In situ guided tissue regeneration in musculoskeletal diseases and aging

Abstract

In situ guided tissue regeneration, also addressed as in situ tissue engineering or endogenous regeneration, has a great potential for population-wide “minimal invasive” applications. During the last two decades, tissue engineering has been developed with remarkable in vitro and preclinical success but still the number of applications in clinical routine is extremely small. Moreover, the vision of population-wide applications of ex vivo tissue engineered constructs based on cells, growth and differentiation factors and scaffolds, must probably be deemed unrealistic for economic and regulation-related issues. Hence, the progress made in this respect will be mostly applicable to a fraction of post-traumatic or post-surgery situations such as big tissue defects due to tumor manifestation. Minimally invasive procedures would probably qualify for a broader application and ideally would only require off the shelf standardized products without cells. Such products should mimic the microenvironment of regenerating tissues and make use of the endogenous tissue regeneration capacities. Functionally, the chemotaxis of regenerative cells, their amplification as a transient amplifying pool and their concerted differentiation and remodeling should be addressed. This is especially important because the main target populations for such applications are the elderly and diseased. The quality of regenerative cells is impaired in such organisms and high levels of inhibitors also interfere with regeneration and healing. In metabolic bone diseases like osteoporosis, it is already known that antagonists for inhibitors such as activin and sclerostin enhance bone formation. Implementing such strategies into applications for in situ guided tissue regeneration should greatly enhance the efficacy of tailored procedures in the future.

Mesenchymal Stem/Stromal Cells: A New ''Cells as Drugs'' Paradigm. Efficacy and Critical Aspects in Cell Therapy

“…In particular, over time, in rodents, monkeys and human BMSCs show a decline in terms of differentiation properties, and the same impairment was demonstrated also for ASCs [130]. Even though debate continues, it is accepted that the difference in MSCs during aging is due to both extrinsic and intrinsic factors, such as genetic background and epigenetic changes [131]. Mansilla et al [132] proposed that some clinical situations like lipodystrophic syndromes, progeria, and more generally aging could be the consequence of a progressive and persistent stem cell exhaustion syndrome.…”

“…Moreover, in older age and in the presence of osteoporosis, mesenchymal precursors tend to follow the adipogenic pathway instead of the osteogenic one [131]. Furthermore the reduction in BMSCs with aging leads to impaired osteogenesis and bone formation.…”

Cellular therapy in bone-tendon interface regeneration

“…Others have taken a more humble, but still ambitious approach to accelerate the implementation of regenerative medicine strategies into clinical care. "Facilitated endogenous repair," 106 also referred to as "in situ guided tissue regeneration," 107 is an approach to tissue engineering that avoids ex vivo culture of autologous cells and the use of manufactured scaffolds, thereby minimizing costs and the number of invasive clinical procedures. Part of this approach would involve the use of autologous cells and extracellular matrices procured, processed, and re-implanted intraoperatively.…”

Biomedizin in der Thoraxchirurgie: eine Standortbestimmung

“…In this review, the clinical background and the tissue-specific basics of tracheobronchial biomedicine are presented. knorpelersatz) und wird hierdurch in einzelnen Anwendungsbereichen möglicherweise in Zukunft Alternativen zur von chronischem Spenderorganmangel geprägten Organtransplantation entwickeln [2,3]. Für den Bereich der Thoraxchirurgie gibt esabgesehen von onkologischer Forschungbiomedizinische Entwicklungen für den Luftröhrenersatz und in deutlich geringerer Zahl für den Lungen-und Brustwandersatz.…”