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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

Injectable cryogels for cell transplantation. (A) Gelation process of cryogels; (B) SEM of highly porous PEG cryogels; (C) Microscopic images of microhydrogels (fluorescently stained by Nile red for enhanced visualization) and the microcryogels with different shapes before and after injection (scale bar = 500 μm); (D) Images demonstrating ability of an individual rhodamine-gelatin cryogel to be compressed between forceps (dashed white line) to large strain, followed by release and resumption of its original shape (Koshy et al., 2014); (E) Primed 3D microniches that can be injected into mouse hindlimb; (F) Representative photographs of sham, blank GMs (gelatin microniches), free hMSCs (105), hMSCs (105) within GMs (GMs + hMSCs), and free hMSCs (106) at 7 and 28 days after treatment (Li et al., 2014). (Images are reproduced with the permission from Li et al. (2014) and Koshy et al. (2014))
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Fig2: Injectable cryogels for cell transplantation. (A) Gelation process of cryogels; (B) SEM of highly porous PEG cryogels; (C) Microscopic images of microhydrogels (fluorescently stained by Nile red for enhanced visualization) and the microcryogels with different shapes before and after injection (scale bar = 500 μm); (D) Images demonstrating ability of an individual rhodamine-gelatin cryogel to be compressed between forceps (dashed white line) to large strain, followed by release and resumption of its original shape (Koshy et al., 2014); (E) Primed 3D microniches that can be injected into mouse hindlimb; (F) Representative photographs of sham, blank GMs (gelatin microniches), free hMSCs (105), hMSCs (105) within GMs (GMs + hMSCs), and free hMSCs (106) at 7 and 28 days after treatment (Li et al., 2014). (Images are reproduced with the permission from Li et al. (2014) and Koshy et al. (2014))

Mentions: As alternatives to hydrogel, scaffolds with relatively larger pores such as cryogel are suitable for cell loading, hence avoiding cell damage during gelation of hydrogel; and also providing sufficient space for cell proliferation (Li et al., 2014). The macro-porous cryogels are mechanically stronger scaffolds with pre-defined size and shape, which enable automatic and homogeneous cell loading and function as injectable cell delivery vehicles. Cells can be primed in vitro before transplantation into lesion area to facilitate long-term therapeutic effect, in which ECM accumulation and cell-cell interactions construct a favorable cellular microenvironment and therefore avoid immediate exposure of transplanted cells to ischemic and inflammatory environment in vivo. To realize this purpose, Koshy et al. developed an injectable, porous and cell-responsive gelatin cryogel that could withstand large strain from forceps compression, without obvious deformation, making injection easier to handle. Li et al. have developed poly-ethylene-glycol (PEG) and gelatin microcryogel systems (from 200–800 μm in diameter) that could be site-directed injected in vivo without significant damage to loaded fibroblasts or MSCs (Liu et al., 2014) (Fig. 2B and 2C). The cell carriers were applied to treat hind limb ischemia in mice. After priming the seeded MSCs in vitro for 2 days, the 3D microscale cellular niches were deposited with ECM essential for cell survival. The microcryogels also protected the cells from mechanical damage during injection and provided cell retention in vivo. Ultimately, only one-tenth of cells compared to that used in conventional free cell therapy were required to achieve even better treatment outcomes as shown by fluorescent imaging of blood perfusion in ischemic hind limb (Li et al., 2014) (Fig. 2E and 2F).Figure 2


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

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

Injectable cryogels for cell transplantation. (A) Gelation process of cryogels; (B) SEM of highly porous PEG cryogels; (C) Microscopic images of microhydrogels (fluorescently stained by Nile red for enhanced visualization) and the microcryogels with different shapes before and after injection (scale bar = 500 μm); (D) Images demonstrating ability of an individual rhodamine-gelatin cryogel to be compressed between forceps (dashed white line) to large strain, followed by release and resumption of its original shape (Koshy et al., 2014); (E) Primed 3D microniches that can be injected into mouse hindlimb; (F) Representative photographs of sham, blank GMs (gelatin microniches), free hMSCs (105), hMSCs (105) within GMs (GMs + hMSCs), and free hMSCs (106) at 7 and 28 days after treatment (Li et al., 2014). (Images are reproduced with the permission from Li et al. (2014) and Koshy et al. (2014))
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig2: Injectable cryogels for cell transplantation. (A) Gelation process of cryogels; (B) SEM of highly porous PEG cryogels; (C) Microscopic images of microhydrogels (fluorescently stained by Nile red for enhanced visualization) and the microcryogels with different shapes before and after injection (scale bar = 500 μm); (D) Images demonstrating ability of an individual rhodamine-gelatin cryogel to be compressed between forceps (dashed white line) to large strain, followed by release and resumption of its original shape (Koshy et al., 2014); (E) Primed 3D microniches that can be injected into mouse hindlimb; (F) Representative photographs of sham, blank GMs (gelatin microniches), free hMSCs (105), hMSCs (105) within GMs (GMs + hMSCs), and free hMSCs (106) at 7 and 28 days after treatment (Li et al., 2014). (Images are reproduced with the permission from Li et al. (2014) and Koshy et al. (2014))
Mentions: As alternatives to hydrogel, scaffolds with relatively larger pores such as cryogel are suitable for cell loading, hence avoiding cell damage during gelation of hydrogel; and also providing sufficient space for cell proliferation (Li et al., 2014). The macro-porous cryogels are mechanically stronger scaffolds with pre-defined size and shape, which enable automatic and homogeneous cell loading and function as injectable cell delivery vehicles. Cells can be primed in vitro before transplantation into lesion area to facilitate long-term therapeutic effect, in which ECM accumulation and cell-cell interactions construct a favorable cellular microenvironment and therefore avoid immediate exposure of transplanted cells to ischemic and inflammatory environment in vivo. To realize this purpose, Koshy et al. developed an injectable, porous and cell-responsive gelatin cryogel that could withstand large strain from forceps compression, without obvious deformation, making injection easier to handle. Li et al. have developed poly-ethylene-glycol (PEG) and gelatin microcryogel systems (from 200–800 μm in diameter) that could be site-directed injected in vivo without significant damage to loaded fibroblasts or MSCs (Liu et al., 2014) (Fig. 2B and 2C). The cell carriers were applied to treat hind limb ischemia in mice. After priming the seeded MSCs in vitro for 2 days, the 3D microscale cellular niches were deposited with ECM essential for cell survival. The microcryogels also protected the cells from mechanical damage during injection and provided cell retention in vivo. Ultimately, only one-tenth of cells compared to that used in conventional free cell therapy were required to achieve even better treatment outcomes as shown by fluorescent imaging of blood perfusion in ischemic hind limb (Li et al., 2014) (Fig. 2E and 2F).Figure 2

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