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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

Immunoisolation principles based on biomaterials and devices currently used as barriers. (A) Principle of immunoisolation by a microcapsule. The semipermeable membrane allows diffusion of molecules such as nutrients, glucose, oxygen, and insulin, and protects the graft from effector molecules of host immune system (Juarez, 2014); (B) Conventional and novel encapsulation devices used for cell immunoisolation (Nafea et al., 2011); (C) A monodispersed cell-laden microbead fabrication method by using axisymmetric flow-focusing devices (Kang et al., 2014); (D) Principle of bioartificial livers. Plasma transfers nutrients and oxygen to hepatocyte-housing compartment across membrane to maintain cell viability. Toxins in plasma are eliminated by hepatocytes via hepatic metabolism. Metabolic substances are returned to blood steam; (E and F) Exchange principles between hepatocytes and plasma or blood in the two types of bioartifical liver devices (Carpentier et al. 2009). (Images are reproduced with the permission from Juarez (2014), Nafea et al. (2011), Carpentier et al. (2009) and Kang et al. (2014))
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Fig3: Immunoisolation principles based on biomaterials and devices currently used as barriers. (A) Principle of immunoisolation by a microcapsule. The semipermeable membrane allows diffusion of molecules such as nutrients, glucose, oxygen, and insulin, and protects the graft from effector molecules of host immune system (Juarez, 2014); (B) Conventional and novel encapsulation devices used for cell immunoisolation (Nafea et al., 2011); (C) A monodispersed cell-laden microbead fabrication method by using axisymmetric flow-focusing devices (Kang et al., 2014); (D) Principle of bioartificial livers. Plasma transfers nutrients and oxygen to hepatocyte-housing compartment across membrane to maintain cell viability. Toxins in plasma are eliminated by hepatocytes via hepatic metabolism. Metabolic substances are returned to blood steam; (E and F) Exchange principles between hepatocytes and plasma or blood in the two types of bioartifical liver devices (Carpentier et al. 2009). (Images are reproduced with the permission from Juarez (2014), Nafea et al. (2011), Carpentier et al. (2009) and Kang et al. (2014))

Mentions: Immune rejection is primarily due to hyperacute rejection (HAR) where host antibodies target antigens on the surfaces of the transplanted cells (Krishnamurthy and Gimi, 2011), and sequentially activate immune response to eliminate those cells. Without survival at the lesion site, transplanted cells cannot exert therapeutic functions. With respect to this, transplanted cells should be protected from surrounding environment to hinder host immune system’s accessibility to engrafts. Clinically, immunosuppressant is commonly applied to prevent immune rejection of transplanted organs or cells in patients, but long-term usage can render recipients vulnerable to infection, as well as susceptible to tumorigenesis (Hernandez et al., 2010). Alternatively, cells can be encapsulated within a semipermeable polymeric membrane to eliminate HAR by preventing cell-host contact (van der Windt et al., 2007). The semipermeable membrane physically permits bi-directional diffusion of small molecules (e.g. oxygen, carbon dioxide, cellular nutrients and growth factors, cellular waste products, ions, and therapeutic molecules secreted by entrapped cells) between host and transplants, while isolates encapsulated cells from host immune cells (e.g. neutrophils and macrophages), and prevents recognition of transplanted cells as foreign objects by antibodies and complements of the recipient’s immune system (Juarez, 2014) (Fig. 3A). Therefore, it is not necessary for recipients to use immunosuppressant, thus eliminating the severe side effects and undesired complications (Orive et al., 2003; Hunt and Grover, 2010). Materials providing protection to cells are desirable in immunoisolated therapy, in which xenograft cells or tissues are encapsulated and isolated from host immune system to ensure cell survival and clinical outcomes. To serve this purpose, non-adhesive microporous scaffolds or membranes fabricated from naturally derived polymers (e.g. alginate (De Vos et al., 1997; Omer et al., 2005; Lacy et al., 1991), and agarose (Schneider et al., 2001; Wong and Chang, 1991)) are desirable. These biomaterials are designed to isolate surrounding tissues, thereby making transplanted cells inaccessible to host immune system and increasing the probability of xenograft survival. By enclosing a transplant with a semipermeable barrier, an ‘artificial immunoprivileged site’ could be created to shield engraft from destruction of host immune system (Paul et al., 2009; Antosiak-Iwanska et al., 2009). Such protective strategy for cells/tissues transplantation has been demonstrated efficient in pathological reversal of many diseases, such as central nervous system diseases, diabetes mellitus, hepatic diseases, amyotrophic lateral sclerosis, hemophilia, hypothyroidism, and cardiovascular diseases (Zhang et al., 2008; Grandoso et al., 2007; Colton, 1995; Desai et al., 2000; Sellitto et al., 1995). As one of the excellent examples of biomaterials functioning as barrier, porcine islets encapsulated in non-degradable alginate were delivered into small or large non-human primates with diabetes to maintain normoglycaemia for as long as 2.4 years (O’Sullivan et al., 2011).Figure 3


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

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

Immunoisolation principles based on biomaterials and devices currently used as barriers. (A) Principle of immunoisolation by a microcapsule. The semipermeable membrane allows diffusion of molecules such as nutrients, glucose, oxygen, and insulin, and protects the graft from effector molecules of host immune system (Juarez, 2014); (B) Conventional and novel encapsulation devices used for cell immunoisolation (Nafea et al., 2011); (C) A monodispersed cell-laden microbead fabrication method by using axisymmetric flow-focusing devices (Kang et al., 2014); (D) Principle of bioartificial livers. Plasma transfers nutrients and oxygen to hepatocyte-housing compartment across membrane to maintain cell viability. Toxins in plasma are eliminated by hepatocytes via hepatic metabolism. Metabolic substances are returned to blood steam; (E and F) Exchange principles between hepatocytes and plasma or blood in the two types of bioartifical liver devices (Carpentier et al. 2009). (Images are reproduced with the permission from Juarez (2014), Nafea et al. (2011), Carpentier et al. (2009) and Kang et al. (2014))
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig3: Immunoisolation principles based on biomaterials and devices currently used as barriers. (A) Principle of immunoisolation by a microcapsule. The semipermeable membrane allows diffusion of molecules such as nutrients, glucose, oxygen, and insulin, and protects the graft from effector molecules of host immune system (Juarez, 2014); (B) Conventional and novel encapsulation devices used for cell immunoisolation (Nafea et al., 2011); (C) A monodispersed cell-laden microbead fabrication method by using axisymmetric flow-focusing devices (Kang et al., 2014); (D) Principle of bioartificial livers. Plasma transfers nutrients and oxygen to hepatocyte-housing compartment across membrane to maintain cell viability. Toxins in plasma are eliminated by hepatocytes via hepatic metabolism. Metabolic substances are returned to blood steam; (E and F) Exchange principles between hepatocytes and plasma or blood in the two types of bioartifical liver devices (Carpentier et al. 2009). (Images are reproduced with the permission from Juarez (2014), Nafea et al. (2011), Carpentier et al. (2009) and Kang et al. (2014))
Mentions: Immune rejection is primarily due to hyperacute rejection (HAR) where host antibodies target antigens on the surfaces of the transplanted cells (Krishnamurthy and Gimi, 2011), and sequentially activate immune response to eliminate those cells. Without survival at the lesion site, transplanted cells cannot exert therapeutic functions. With respect to this, transplanted cells should be protected from surrounding environment to hinder host immune system’s accessibility to engrafts. Clinically, immunosuppressant is commonly applied to prevent immune rejection of transplanted organs or cells in patients, but long-term usage can render recipients vulnerable to infection, as well as susceptible to tumorigenesis (Hernandez et al., 2010). Alternatively, cells can be encapsulated within a semipermeable polymeric membrane to eliminate HAR by preventing cell-host contact (van der Windt et al., 2007). The semipermeable membrane physically permits bi-directional diffusion of small molecules (e.g. oxygen, carbon dioxide, cellular nutrients and growth factors, cellular waste products, ions, and therapeutic molecules secreted by entrapped cells) between host and transplants, while isolates encapsulated cells from host immune cells (e.g. neutrophils and macrophages), and prevents recognition of transplanted cells as foreign objects by antibodies and complements of the recipient’s immune system (Juarez, 2014) (Fig. 3A). Therefore, it is not necessary for recipients to use immunosuppressant, thus eliminating the severe side effects and undesired complications (Orive et al., 2003; Hunt and Grover, 2010). Materials providing protection to cells are desirable in immunoisolated therapy, in which xenograft cells or tissues are encapsulated and isolated from host immune system to ensure cell survival and clinical outcomes. To serve this purpose, non-adhesive microporous scaffolds or membranes fabricated from naturally derived polymers (e.g. alginate (De Vos et al., 1997; Omer et al., 2005; Lacy et al., 1991), and agarose (Schneider et al., 2001; Wong and Chang, 1991)) are desirable. These biomaterials are designed to isolate surrounding tissues, thereby making transplanted cells inaccessible to host immune system and increasing the probability of xenograft survival. By enclosing a transplant with a semipermeable barrier, an ‘artificial immunoprivileged site’ could be created to shield engraft from destruction of host immune system (Paul et al., 2009; Antosiak-Iwanska et al., 2009). Such protective strategy for cells/tissues transplantation has been demonstrated efficient in pathological reversal of many diseases, such as central nervous system diseases, diabetes mellitus, hepatic diseases, amyotrophic lateral sclerosis, hemophilia, hypothyroidism, and cardiovascular diseases (Zhang et al., 2008; Grandoso et al., 2007; Colton, 1995; Desai et al., 2000; Sellitto et al., 1995). As one of the excellent examples of biomaterials functioning as barrier, porcine islets encapsulated in non-degradable alginate were delivered into small or large non-human primates with diabetes to maintain normoglycaemia for as long as 2.4 years (O’Sullivan et al., 2011).Figure 3

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