Pros And Cons Of Adult Stem Cells – Regeneration of bone fractures caused by trauma, osteoporosis or tumors is a major problem in our super-aging society. Bone regeneration is a major concern of regenerative medicine In recent years, stem cells have been employed in regenerative medicine with interesting results due to their self-renewal and differentiation capacity. Furthermore, stem cells are capable of secreting bioactive molecules and regulating the behavior of other cells in various host tissues. When stem cells are used, the bone regeneration process can be improved effectively and rapidly To this end, stem cells are incorporated into the biomaterial/scaffold and growth factors to accelerate bone healing at the fracture site. In summary, this review will describe the bone formation and osteogenic differentiation of stem cells. In addition, the role of mesenchymal stem cells for bone repair/regrowth in the field of tissue engineering and their progress in clinical applications will be discussed.

Bone disorders are seen daily in clinical management with significant health, social and economic consequences (Figliomeni et al., 2018). Annually, more than 20 million people are affected by bone loss (Habibovic, 2017). Bone repair after fracture is a complex process characterized by sequential cellular and molecular events regulated by systemic and local factors ( Orbidson et al., 2011 ).

Pros And Cons Of Adult Stem Cells

Although bone fracture repair usually restores the damaged skeletal limb to its pre-injury position, approximately 10% of fractures will not heal normally (Einhorn and Gerstenfeld, 2015). In fact, in some cases, the bone regeneration process may fail due to osteosarcoma, osteoporosis, osteomalacia, osteomyelitis, avascular necrosis and atrophic non-union (Hao et al., 2014; Ferrecini et al., 2018).

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In particular, osteosarcoma and Ewing sarcoma are the two most common types of bone cancer diagnosed in young subjects (Ward et al., 2014). In fact, unlike other tumors that commonly affect elderly people (Togon et al., 2015; Mazzoni et al., 2016, 2017b; Rotondo et al., 2016, 2018), osteosarcoma and Ewing sarcoma mainly affect children/adolescents and It is diagnosed in young people Adults accounted for 56 and 33%, respectively (Ward et al., 2014). Current osteosarcoma treatment includes surgical resection combined with chemotherapy (Harrison et al., 2018). On the other hand, osteoporosis is a chronic disease that leads patients to an increased risk of fractures (Schumacher et al., 2013). This pathology is characterized by high morbidity and mortality in the aging population (Migliaccio et al., 2017). Affected bones can be restored to their normal state in clinical practice using bone grafts, such as auto-grafts, allo-grafts, or xeno-grafts (Rass et al., 2019). Autologous grafts represent the clinical gold standard in improving bone regeneration due to their complete histocompatibility, and osteoinductive and osteoconductive properties (Sypher and Grossman, 1996). However, auto-grafts present some disadvantages from the limited amount of bone resulting from grafting and donor site morbidity. In contrast, allo-grafts and xeno-grafts present an alternative approach to bone grafts because they solve the problem of limited autologous bone supply and do not require an additional surgical site for graft harvesting (Deloy et al., 2007). However, allo- and xeno-grafts present some difficulties, such as donor shortage, high costs, risk of infectious agent transmission or immune response (Ferresini et al., 2018; Ho-Shui-Ling et al., 2018). For these reasons, a more efficient clinical therapeutic strategy is needed To this end, tissue engineering has employed new osteoconductive and osteoinductive biomaterials/scaffolds, stem cells and growth factors to improve bone repair/regrowth (Iaquinta et al., 2019). Stem cells, especially MSCs, can support tissue regeneration/replacement (Kaplan and Dennis) with the secretion of molecules characterized by continuous self-renewal and proliferation, multi-potentiality, anti-inflammatory and immune-modulatory effects. , 2006 ) have been used in clinical applications for more than 20 years, but the characteristics and potential of stem cells for bone repair have not yet been fully characterized ( Jin and Lee, 2018 ). Specifically, stem cells have been considered in many therapeutic areas to repair defective tissues and organs, including bones, ligaments, and the heart (Abdel Meguid et al., 2018). Thus, this review will focus on potential applications for stem cells, specifically MSCs, to improve bone tissue regeneration.

Bone is a tough and highly mobile tissue that supports and protects many parts of the body Furthermore, bone tissue provides an environment for the production of red and white blood cells, plays an important role in mineral homeostasis such as calcium and phosphorus, and provides a solid base for skeletal muscle (Abdel Meguid et al., 2018). Two types of osseous tissue can be identified: hard cortical or compact bone, which represents 80% of bone mass. , and trabecular bone, remains (Vico et al., 2017). Cortical bone is the stiff outer layer of bone, while trabecular bone architecture is organized to optimize load transfer (Bayracter et al., 2004). Trabecular bone can also be found at the ends of long bones, pelvic bones, skulls, ribs, and vertebrae. Moreover, it contains the red bone marrow where hematopoiesis occurs (Gdyczynski et al., 2014; Abdel Meguid et al., 2018).

Cortical and trabecular bones are subject to bone remodeling (see below), a life-long process that plays an important role in bone mass balance and mineral homeostasis ( Tolar et al., 2004 ). Furthermore, bone tissue can be separated into two distinct phases (i) bone matrix and (ii) an organic phase that includes cellular components such as osteoblasts, osteoclasts and osteocytes (Farbod et al., 2014) (Figure 1).

Figure 1. Representation of bone structure Two types of osseous tissue can be identified: compact bone and trabecular bone Bone tissue is a vital, life-changing process that plays an important role in bone mass balance and mineral homeostasis. During bone remodeling, osteoclasts, derived from hematopoietic stem cells, regenerate old or damaged bone. Subsequently, osteoblasts, derived from mesenchymal stem cells, are recruited to the damaged area to replace the bone removed by osteoclasts. Instead, osteoblast-derived osteocytes suspend their activity while buried in the bone matrix.

Stem Cell Research

Bone matrix is ​​a dynamic network that represents the intercellular material of bone tissue It is composed of several organic and inorganic components, such as collagen type I, which is the most abundant protein in bone tissue, elastin, polysaccharides and calcium phosphate (Schönherr and Hausser, 2000; Fujisawa and Tamura, 2012; Farbod et al). ., 2014) The major non-collagenous proteins of the bone matrix are sialoproteins, osteonectin, osteopontin, and osteocalcin (Palmer et al., 2008), which contain aspartic acid (Asp) and glutamic acid (Glu) residues, for calcium ions (Ca). There are more relationships

) due to their charged carboxyl groups (Palmer et al., 2008). Polyglutamic acid segments in bone sialoproteins are responsible for binding to apatite, while a similar role in osteopontin is played by polypartic acid segments (Ganss et al., 1999; Fantner et al., 2007). Osteonectin, a protein rich in the amino acid cysteine, is expressed in high concentrations in the mineral. Osteonectin is involved in osteoblast differentiation and osteoclast activity (Rossett and Bradshaw, 2016). Osteocalcin, also known as bone β-carboxyglutamate protein (BGLAP), is expressed by osteoblasts and is commonly used as a clinical marker of bone turnover (Lambert et al., 2016). Bone matrix can regulate cell proliferation and differentiation through soluble growth factors and cytokines (Rosso et al., 2004). On the other hand, the inorganic component of the bone matrix is ​​an ion reservoir (Weatherholt et al., 2012). Hydroxylapatite [HA; Ca.

In tissue engineering, knowledge of bone nanostructures and interactions between inorganic and organic phases is important for producing biomaterials with structural and functional properties similar to natural bone tissue. Generally, these interactions involve anionic and/or cationic functional groups, which are found in organic matrices and subsequently show strong affinity for calcium or phosphate ions in the bone mineral phase. Anionic functional groups, i.e., carboxyl-containing and calcium-binding moieties, proteins, peptide sequences, single amino acids, and COOH groups, are widely researched chemical groups that play a key role in improving the interaction of inorganic and organic phases. does in synthetic nano-composites for bone regeneration (Farbod et al., 2014).

The majority of bone tissue cells in the organic phase are osteoblasts and osteoclasts (Kartsogiannis and Nag, 2004). Specifically osteoclasts, cells that originate from the myeloid lineage of the hematopoietic precursors of bone marrow and specialize in bone resorption (Charles and Aliprantis, 2014). On the other hand, osteoblasts derived from mesenchymal stem cells (MSCs) from bone marrow, blood and pericytes are involved in bone formation and replace the bone removed by osteoclasts (Sim and Civitelli, 2014). It has been reported that the migration of MSCs to the bone surface is an important step in bone formation and fracture healing Indeed, changes in MSC migration can lead to unstable imbalances However, MSC migration is a complex mechanism whose regulatory mechanisms have not yet been elucidated (Su et al., 2018). Furthermore, other osteoblast-derived cells reside in bone tissue, such as bone lining cells and osteocytes. Bone lining cells cover the surface of bone, where bone resorption or bone formation is not requested (Miller et al., 1989) whereas osteoblast-derived osteocytes suspend their activity after being buried in the matrix. It has

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