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Biomaterials as carrier, barrier and reactor for cell-based regenerative medicine.

Qi C, Yan X, Huang C, Melerzanov A, Du Y - Protein Cell (2015)

Bottom Line: However, challenges such as cell loss, death and immune-rejection after transplantation still persist.Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation.With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, China.

ABSTRACT
Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy. Emerging clinical applications of biomaterial assisted cell therapies further highlight their great promise in regenerative therapy and even cure for complex diseases, which have been failed to realize by conventional therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus

Transplantable biomaterials as cell carriers. (A) Perfusion-based decellularization of whole rat hearts and HE staining at different stages; (B) SEM of cadaveric and decellularized left ventricular (LV) and right ventricular (RV) myocardium, myofibers (mf), characteristic weaves (w), coils (c), struts (s), and dense epicardial fibers (epi) were retained (Ott et al., 2008); (C) General appearance of rat liver during decellularization process at different time points; (D) Ultrastructural characteristics of undifferentiated MSCs (i) and hepatocyte-like cells (ii) in biomatrix scaffold using SEM (Ji et al., 2012); (E) Engineered scaffold containing transplanted cells and growth factors is able to guide tissue regeneration in situ (Borselli et al., 2011); (F) Modification of RGD as morphogens on biomaterials providing cell adhesion ligands to maintain cell viability, and to activate and induce cell migration out of scaffold; (G) Viability of endothelial cells (OECs) that migrated out of scaffolds with no VEGF (blank), VEGF121 or VEGF165 in scaffolds; (H) Proliferation of cells that migrated out of scaffolds, normalized cell number (% of initial) (Silva et al., 2008). [Images are reproduced with the permission from Ott et al. (2008), Ji et al. (2012), Borselli et al. (2011), and Silva et al. (2008)]
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Fig1: Transplantable biomaterials as cell carriers. (A) Perfusion-based decellularization of whole rat hearts and HE staining at different stages; (B) SEM of cadaveric and decellularized left ventricular (LV) and right ventricular (RV) myocardium, myofibers (mf), characteristic weaves (w), coils (c), struts (s), and dense epicardial fibers (epi) were retained (Ott et al., 2008); (C) General appearance of rat liver during decellularization process at different time points; (D) Ultrastructural characteristics of undifferentiated MSCs (i) and hepatocyte-like cells (ii) in biomatrix scaffold using SEM (Ji et al., 2012); (E) Engineered scaffold containing transplanted cells and growth factors is able to guide tissue regeneration in situ (Borselli et al., 2011); (F) Modification of RGD as morphogens on biomaterials providing cell adhesion ligands to maintain cell viability, and to activate and induce cell migration out of scaffold; (G) Viability of endothelial cells (OECs) that migrated out of scaffolds with no VEGF (blank), VEGF121 or VEGF165 in scaffolds; (H) Proliferation of cells that migrated out of scaffolds, normalized cell number (% of initial) (Silva et al., 2008). [Images are reproduced with the permission from Ott et al. (2008), Ji et al. (2012), Borselli et al. (2011), and Silva et al. (2008)]

Mentions: Netoff’s group and Taylor’s group realized recellularization with cardiac or endothelial cells on cardiac ECM produced by decellularization via perfusion (Ott et al., 2008; Badylak et al., 2011). The biomimetic tissues could maintain functional contraction and be electrically stimulated in vitro for 28 days. Taylor’s group further optimized the cell seeding method to obtain more uniform distribution and transplanted the tissue into recipient rats (Badylak et al., 2011). Rats survived after the surgery and no immune reaction was observed until 7 days after transplantation, proving the functionality of the artificial heart in vivo. Similar research had been conducted in liver (Fig. 1A and 1B), where ECM with intact hepatic vasculature system was obtained by decellularization of liver. Ji et al. seeded mesenchymal stromal cells (MSCs) into the scaffold, cultured the artificial tissue in vitro in presence of growth factors to induce MSCs differentiation into hepatic lineage. The resulting tissue exhibited hepatic ultrastructure, which was transplanted into mice with liver failure induced by CCl4. The mice were rescued with liver regeneration thanks to paracrine factors of MSCs-differentiated hepatocytes (Ji et al., 2012) (Fig. 1C and 1D).Figure 1


Biomaterials as carrier, barrier and reactor for cell-based regenerative medicine.

Qi C, Yan X, Huang C, Melerzanov A, Du Y - Protein Cell (2015)

Transplantable biomaterials as cell carriers. (A) Perfusion-based decellularization of whole rat hearts and HE staining at different stages; (B) SEM of cadaveric and decellularized left ventricular (LV) and right ventricular (RV) myocardium, myofibers (mf), characteristic weaves (w), coils (c), struts (s), and dense epicardial fibers (epi) were retained (Ott et al., 2008); (C) General appearance of rat liver during decellularization process at different time points; (D) Ultrastructural characteristics of undifferentiated MSCs (i) and hepatocyte-like cells (ii) in biomatrix scaffold using SEM (Ji et al., 2012); (E) Engineered scaffold containing transplanted cells and growth factors is able to guide tissue regeneration in situ (Borselli et al., 2011); (F) Modification of RGD as morphogens on biomaterials providing cell adhesion ligands to maintain cell viability, and to activate and induce cell migration out of scaffold; (G) Viability of endothelial cells (OECs) that migrated out of scaffolds with no VEGF (blank), VEGF121 or VEGF165 in scaffolds; (H) Proliferation of cells that migrated out of scaffolds, normalized cell number (% of initial) (Silva et al., 2008). [Images are reproduced with the permission from Ott et al. (2008), Ji et al. (2012), Borselli et al. (2011), and Silva et al. (2008)]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: Transplantable biomaterials as cell carriers. (A) Perfusion-based decellularization of whole rat hearts and HE staining at different stages; (B) SEM of cadaveric and decellularized left ventricular (LV) and right ventricular (RV) myocardium, myofibers (mf), characteristic weaves (w), coils (c), struts (s), and dense epicardial fibers (epi) were retained (Ott et al., 2008); (C) General appearance of rat liver during decellularization process at different time points; (D) Ultrastructural characteristics of undifferentiated MSCs (i) and hepatocyte-like cells (ii) in biomatrix scaffold using SEM (Ji et al., 2012); (E) Engineered scaffold containing transplanted cells and growth factors is able to guide tissue regeneration in situ (Borselli et al., 2011); (F) Modification of RGD as morphogens on biomaterials providing cell adhesion ligands to maintain cell viability, and to activate and induce cell migration out of scaffold; (G) Viability of endothelial cells (OECs) that migrated out of scaffolds with no VEGF (blank), VEGF121 or VEGF165 in scaffolds; (H) Proliferation of cells that migrated out of scaffolds, normalized cell number (% of initial) (Silva et al., 2008). [Images are reproduced with the permission from Ott et al. (2008), Ji et al. (2012), Borselli et al. (2011), and Silva et al. (2008)]
Mentions: Netoff’s group and Taylor’s group realized recellularization with cardiac or endothelial cells on cardiac ECM produced by decellularization via perfusion (Ott et al., 2008; Badylak et al., 2011). The biomimetic tissues could maintain functional contraction and be electrically stimulated in vitro for 28 days. Taylor’s group further optimized the cell seeding method to obtain more uniform distribution and transplanted the tissue into recipient rats (Badylak et al., 2011). Rats survived after the surgery and no immune reaction was observed until 7 days after transplantation, proving the functionality of the artificial heart in vivo. Similar research had been conducted in liver (Fig. 1A and 1B), where ECM with intact hepatic vasculature system was obtained by decellularization of liver. Ji et al. seeded mesenchymal stromal cells (MSCs) into the scaffold, cultured the artificial tissue in vitro in presence of growth factors to induce MSCs differentiation into hepatic lineage. The resulting tissue exhibited hepatic ultrastructure, which was transplanted into mice with liver failure induced by CCl4. The mice were rescued with liver regeneration thanks to paracrine factors of MSCs-differentiated hepatocytes (Ji et al., 2012) (Fig. 1C and 1D).Figure 1

Bottom Line: However, challenges such as cell loss, death and immune-rejection after transplantation still persist.Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation.With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, 100084, China.

ABSTRACT
Cell therapy has achieved tremendous success in regenerative medicine in the past several decades. However, challenges such as cell loss, death and immune-rejection after transplantation still persist. Biomaterials have been designed as carriers to deliver cells to desirable region for local tissue regeneration; as barriers to protect transplanted cells from host immune attack; or as reactors to stimulate host cell recruitment, homing and differentiation. With the assistance of biomaterials, improvement in treatment efficiency has been demonstrated in numerous animal models of degenerative diseases compared with routine free cell-based therapy. Emerging clinical applications of biomaterial assisted cell therapies further highlight their great promise in regenerative therapy and even cure for complex diseases, which have been failed to realize by conventional therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus