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Abstract
Effective regeneration of bone defects often presents significant challenges, particularly in patients with decreased tissue regeneration capacity due to extensive trauma, disease, and/or advanced age. A number of studies have focused on enhancing bone regeneration by applying mesenchymal stromal cells (MSCs) or MSC-based bone tissue engineering strategies. However, translation of these approaches from basic research findings to clinical use has been hampered by the limited understanding of MSC therapeutic actions and complexities, as well as costs related to the manufacturing, regulatory approval, and clinical use of living cells and engineered tissues. More recently, a shift from the view of MSCs directly contributing to tissue regeneration toward appreciating MSCs as “cell factories” that secrete a variety of bioactive molecules and extracellular vesicles with trophic and immunomodulatory activities has steered research into new MSC-based, “cell-free” therapeutic modalities. The current review recapitulates recent developments, challenges, and future perspectives of these various MSC-based bone tissue engineering and regeneration strategies.
Highlights
Regeneration of bone defects often presents significant challenges, in patients with decreased tissue regeneration capacity due to extensive tissue damage, disease, advanced age, and confounding systemic and lifestyle factors (Gruber et al, 2006; Borrelli et al, 2012)
A shift from the view of mesenchymal stromal cells (MSCs) as being cells that directly contribute to new tissue formation toward seeing MSCs as “medicinal cell factories” that secrete a variety of bioactive molecules with trophic and immunomodulatory activities has steered the research into MSC secretome for bone regeneration (Hofer and Tuan, 2016; Caplan, 2017)
Based on the positive outcomes of preclinical studies (Bruder et al, 1998; Petite et al, 2000; Arinzeh et al, 2003; GraneroMoltó et al, 2009; Caralla et al, 2013; Chung et al, 2015), freshly isolated bone marrow mononuclear cells (MNCs) as well as culture-expanded MSCs from bone marrow, adipose tissue, and dental pulp were evaluated clinically in order to enhance the healing of bone fractures, non-unions, various jaw bone defects, and to prevent bone degradation in femoral head osteonecrosis (Table 1) (Stegemann et al, 2014)
Summary
Regeneration of bone defects often presents significant challenges, in patients with decreased tissue regeneration capacity due to extensive tissue damage, disease, advanced age, and confounding systemic and lifestyle factors (Gruber et al, 2006; Borrelli et al, 2012). Based on the positive outcomes of preclinical studies (Bruder et al, 1998; Petite et al, 2000; Arinzeh et al, 2003; GraneroMoltó et al, 2009; Caralla et al, 2013; Chung et al, 2015), freshly isolated bone marrow mononuclear cells (MNCs) as well as culture-expanded MSCs from bone marrow, adipose tissue, and dental pulp were evaluated clinically in order to enhance the healing of bone fractures, non-unions, various jaw bone defects, and to prevent bone degradation in femoral head osteonecrosis (Table 1) (Stegemann et al, 2014).
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