Pub Date : 2013-12-30DOI: 10.2174/1875043501306010026
M. Kaveh, A. Mehdi, A. Farid, Rastegar Tayebeh, A. Hamidreza, Abbasi Majid, L. Mostafa, Koruji Morteza, Sargolzaei Aval Fereidon, Salehi Majid, Mohammadi Rad Mosleh
Objectives: In the previous study, although it has been shown that intramyocardial injection of human umbilical cord matrix stem cell (hUCM) improved cardiac function 4 weeks post MI, but angiogenesis has not been observed. Angiogenesis and replacing lost cardiomyocytes with new, live cardiomyocytes are considered as two key agents in cardiac repair. To achieve the above two factors we examined the effects of combination of stem cell and angiogenic therapy approaches by simultaneously injection of hUCM-derived cardiomyocytes with vascular endothelial growth factor (VEGF) in cardiac repair. Methods: MI-induced animals(by ligation of LAD) received 50 µl PBS, 5 × 10 6 differentiated hUCM cells (dhUCM), 5µg VEGF in normal saline and 5 × 10 6 dhUCM cells combined with 5µg VEGF in normal saline, intramyocardialy. MI group, with no other intervention, served as a control group. We were assessed survival, migration and integration of dhUCM cells, as well as angiogenesis eight weeks post MI induction. Results: Eight weeks post MI, although dhUCM and VEGF groups have shown that LVEF and LVFS improved significantly, but animals in dhUCM+VEGF group have the highest rise in LVEF and LVFS in comparison to the other MI-induced groups (p<0.05). Histological and morphological analysis have revealed that myocardium of animals in dhUCM+VEGF group have the highest vascular density and the lowest fibrosis tissue in comparison to the other MI- induced groups (p<0.05). Immunohistological assessments revealed that transplanted dhUCM cells have survived, migrated to infarcted area and integrated with recipient cardiac tissue. Conclusion: we have found that intramyocardial administration of dhUCM cells combined with VEGF improved cardiac function, enhanced angiogenesis and reduced fibrosis tissue formation after MI, eight weeks post MI.
{"title":"Restoration of Heart Function Using Transplantation of Human Umbilical Cord Matrix-Derived Cardiomyocytes and Vascular Endothelial Growth Factor","authors":"M. Kaveh, A. Mehdi, A. Farid, Rastegar Tayebeh, A. Hamidreza, Abbasi Majid, L. Mostafa, Koruji Morteza, Sargolzaei Aval Fereidon, Salehi Majid, Mohammadi Rad Mosleh","doi":"10.2174/1875043501306010026","DOIUrl":"https://doi.org/10.2174/1875043501306010026","url":null,"abstract":"Objectives: In the previous study, although it has been shown that intramyocardial injection of human umbilical cord matrix stem cell (hUCM) improved cardiac function 4 weeks post MI, but angiogenesis has not been observed. Angiogenesis and replacing lost cardiomyocytes with new, live cardiomyocytes are considered as two key agents in cardiac repair. To achieve the above two factors we examined the effects of combination of stem cell and angiogenic therapy approaches by simultaneously injection of hUCM-derived cardiomyocytes with vascular endothelial growth factor (VEGF) in cardiac repair. Methods: MI-induced animals(by ligation of LAD) received 50 µl PBS, 5 × 10 6 differentiated hUCM cells (dhUCM), 5µg VEGF in normal saline and 5 × 10 6 dhUCM cells combined with 5µg VEGF in normal saline, intramyocardialy. MI group, with no other intervention, served as a control group. We were assessed survival, migration and integration of dhUCM cells, as well as angiogenesis eight weeks post MI induction. Results: Eight weeks post MI, although dhUCM and VEGF groups have shown that LVEF and LVFS improved significantly, but animals in dhUCM+VEGF group have the highest rise in LVEF and LVFS in comparison to the other MI-induced groups (p<0.05). Histological and morphological analysis have revealed that myocardium of animals in dhUCM+VEGF group have the highest vascular density and the lowest fibrosis tissue in comparison to the other MI- induced groups (p<0.05). Immunohistological assessments revealed that transplanted dhUCM cells have survived, migrated to infarcted area and integrated with recipient cardiac tissue. Conclusion: we have found that intramyocardial administration of dhUCM cells combined with VEGF improved cardiac function, enhanced angiogenesis and reduced fibrosis tissue formation after MI, eight weeks post MI.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"6 1","pages":"26-36"},"PeriodicalIF":0.0,"publicationDate":"2013-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-10-31DOI: 10.2174/1875043501306010012
M. Iacono, R. Anzalone, S. Corrao, T. Corsello, C. Loreto, S. Sansalone, M. Sergio, M. Cimador, M. Giuffré, F. Farina, G. Rocca
End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viability of isolated hepatocytes and, when applicable, the limited differentiation of stem cells (when hepatocyte-like cells are derived from hepatic or extra-hepatic progenitor populations). In recent years, perinatal stem cells have been proposed as reliable cellular populations which may be successfully used to derive hepatocyte-like cells. These cells feature key advantages over other adult stem cells: may be easily sourced from the tissues of origin, can be expanded ex vivo to obtain high cell numbers, may be differentiated towards hepatocyte-like cells. In addition, these cells feature relevant immunomodulatory and anti-inflammatory activities, and their sourcing is not limited by ethical concerns In the present review we analyze the molecular basis of hepatocyte biology and development, and discuss the recent advances in deriving hapatocyte-like cells from perinatal stem cells. Very recent papers on mesenchymal stem cells derived from bone marrow and adipose tissues are also comparatively discussed as prototypes of the use of adult extra- hepatic stem cells. In our opinion, perinatal stem cells do represent a promising tool for liver regenerative medicine, and recent research reports further strengthened this perception and fostered further efforts by multiple research groups
{"title":"Recent advances in derivation of functional hepatocytes from placental stem cells","authors":"M. Iacono, R. Anzalone, S. Corrao, T. Corsello, C. Loreto, S. Sansalone, M. Sergio, M. Cimador, M. Giuffré, F. Farina, G. Rocca","doi":"10.2174/1875043501306010012","DOIUrl":"https://doi.org/10.2174/1875043501306010012","url":null,"abstract":"End-stage liver diseases are one of the leading causes of death in the world. Often orthotopic liver transplantation represents the final therapeutic choice. The limits of this approach are the scarcity of donor livers available, and the many side effects related to the administration of immune suppressants to the patients. Cellular therapy for liver diseases is increasingly being viewed as a promising strategy to provide hepatocytes to replenish the parenchymal cells of the organ. This technique suffers of some important limitations, such as the difficulty in isolating sufficient cell numbers (e.g. when adult or foetal hepatocytes are used for transplantation), the limited viability of isolated hepatocytes and, when applicable, the limited differentiation of stem cells (when hepatocyte-like cells are derived from hepatic or extra-hepatic progenitor populations). In recent years, perinatal stem cells have been proposed as reliable cellular populations which may be successfully used to derive hepatocyte-like cells. These cells feature key advantages over other adult stem cells: may be easily sourced from the tissues of origin, can be expanded ex vivo to obtain high cell numbers, may be differentiated towards hepatocyte-like cells. In addition, these cells feature relevant immunomodulatory and anti-inflammatory activities, and their sourcing is not limited by ethical concerns In the present review we analyze the molecular basis of hepatocyte biology and development, and discuss the recent advances in deriving hapatocyte-like cells from perinatal stem cells. Very recent papers on mesenchymal stem cells derived from bone marrow and adipose tissues are also comparatively discussed as prototypes of the use of adult extra- hepatic stem cells. In our opinion, perinatal stem cells do represent a promising tool for liver regenerative medicine, and recent research reports further strengthened this perception and fostered further efforts by multiple research groups","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"6 1","pages":"12-25"},"PeriodicalIF":0.0,"publicationDate":"2013-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2013-07-29DOI: 10.2174/1875043501306010001
U. Galili
This review describes a novel method for accelerating tissue regeneration by ! -gal nanoparticles and proposes methods for ! -gal nanoparticles mediated increased efficacy of biomaterials used in tissue engineering. ! -Gal nanoparti- cles present multiple ! -gal epitopes (Gal! 1-3Gal" 1-4GlcNAc-R) that bind the most abundant natural antibody in all hu- mans- the anti-Gal antibody, constituting ~1% of immunoglobulins. Anti-Gal/! -gal nanoparticles interaction generates chemotactic complement cleavage peptides that induce rapid and extensive recruitment of macrophages. The subsequent interaction between the Fc portion of anti-Gal coating ! -gal nanoparticles and Fc# receptors on macrophages activates these cells to produce cytokines/growth factors that promote tissue regeneration and recruit stem cells. Intradermal injec- tion of ! -gal nanoparticles induces localized extensive recruitment and activation of macrophages. These macrophages disappear within 3 weeks without altering normal skin architecture. Application of ! -gal nanoparticles onto wounds of anti-Gal producing animals reduces healing time by 40-70%. ! -Gal nanoparticles injected into ischemic myocardium in- duce extensive recruitment of macrophages that secrete cytokines preserving the structure of the ischemic tissue. These macrophages may recruit progenitor cells and/or stem cells that are guided by myocardial microenvironment and extracel- lular matrix to differentiate into cardiomyocytes. ! -Gal nanoparticles applied to nerve injures will recruit macrophages that can promote angiogenesis required for induction of axonal sprouting and thus may regenerate the severed nerve. In tissue engineering, incorporation of ! -gal nanoparticles into decellularized tissue and organ implants may improve in vivo regeneration and restore biological function of implants because of accelerated recruitment of macrophages and stem cells. This review describes a novel method for recruitment and activation of macrophages within injured tissues by ! -gal nanoparticles. The review further proposes the use of these nanoparticles in biomaterials for tissue engineering, in order to accelerate and increase the efficacy of tissue repair and regeneration processes. The method is based on harnessing the immunological potential of the natural anti-Gal antibody, which is the most abundant natural antibody in humans. Anti-Gal interacts specifically with a carbohydrate antigen called "the ! -gal epitope" with the structure Gal! 1-3Gal" 1- 4GlcNAc-R. Nanoparticles presenting multiple ! -gal epi- topes and called ! -gal nanoparticles introduce these epitopes into injury sites or into biomaterials. The interaction of anti- Gal with ! -gal epitopes on ! -gal nanoparticles activates the complement system for rapid chemotactic recruitment of macrophages. This interaction further induces pro-healing functions in the recruited macrophages which may recruit stem cells. The review describes studies on the efficacy of anti-Gal/
{"title":"Macrophages Recruitment and Activation by α-gal NanoparticlesAccelerate Regeneration and Can Improve Biomaterials Efficacy in TissueEngineering","authors":"U. Galili","doi":"10.2174/1875043501306010001","DOIUrl":"https://doi.org/10.2174/1875043501306010001","url":null,"abstract":"This review describes a novel method for accelerating tissue regeneration by ! -gal nanoparticles and proposes methods for ! -gal nanoparticles mediated increased efficacy of biomaterials used in tissue engineering. ! -Gal nanoparti- cles present multiple ! -gal epitopes (Gal! 1-3Gal\" 1-4GlcNAc-R) that bind the most abundant natural antibody in all hu- mans- the anti-Gal antibody, constituting ~1% of immunoglobulins. Anti-Gal/! -gal nanoparticles interaction generates chemotactic complement cleavage peptides that induce rapid and extensive recruitment of macrophages. The subsequent interaction between the Fc portion of anti-Gal coating ! -gal nanoparticles and Fc# receptors on macrophages activates these cells to produce cytokines/growth factors that promote tissue regeneration and recruit stem cells. Intradermal injec- tion of ! -gal nanoparticles induces localized extensive recruitment and activation of macrophages. These macrophages disappear within 3 weeks without altering normal skin architecture. Application of ! -gal nanoparticles onto wounds of anti-Gal producing animals reduces healing time by 40-70%. ! -Gal nanoparticles injected into ischemic myocardium in- duce extensive recruitment of macrophages that secrete cytokines preserving the structure of the ischemic tissue. These macrophages may recruit progenitor cells and/or stem cells that are guided by myocardial microenvironment and extracel- lular matrix to differentiate into cardiomyocytes. ! -Gal nanoparticles applied to nerve injures will recruit macrophages that can promote angiogenesis required for induction of axonal sprouting and thus may regenerate the severed nerve. In tissue engineering, incorporation of ! -gal nanoparticles into decellularized tissue and organ implants may improve in vivo regeneration and restore biological function of implants because of accelerated recruitment of macrophages and stem cells. This review describes a novel method for recruitment and activation of macrophages within injured tissues by ! -gal nanoparticles. The review further proposes the use of these nanoparticles in biomaterials for tissue engineering, in order to accelerate and increase the efficacy of tissue repair and regeneration processes. The method is based on harnessing the immunological potential of the natural anti-Gal antibody, which is the most abundant natural antibody in humans. Anti-Gal interacts specifically with a carbohydrate antigen called \"the ! -gal epitope\" with the structure Gal! 1-3Gal\" 1- 4GlcNAc-R. Nanoparticles presenting multiple ! -gal epi- topes and called ! -gal nanoparticles introduce these epitopes into injury sites or into biomaterials. The interaction of anti- Gal with ! -gal epitopes on ! -gal nanoparticles activates the complement system for rapid chemotactic recruitment of macrophages. This interaction further induces pro-healing functions in the recruited macrophages which may recruit stem cells. The review describes studies on the efficacy of anti-Gal/","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"6 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2013-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-11-30DOI: 10.2174/1875043501205010059
Bano Subia, Sunandan Mukherjee, R. Bahadur, V. Correlo, L. ReisRui, R. Sabarinathan, K. Sekar, S. Kundu
Biomaterial science provides a platform for the development of bio-artificial implants. Growth or development of engineered tissues for the purpose of repairing, restoring and enhancing the function of a damaged tissue or organ needs designed biomaterials. The most studied tissue engineering strategy consists on using cells growth factors and temporary three-dimensional (3D) porous scaffolds. 3D scaffolds play a very important role in the success of tissue engineering and regenerative medicine. They provide structural support for cells to proliferate and maintain their differentiated phenotype and permit the convenient delivery of cells into the patients. Several features of scaffold can influence the cell growth and its functions. The artificial extracellular matrices can be produced from different biomaterials including ceramics, natural or synthetic polymers and composites. Recent discoveries and innovations in this emerging field adopt varieties of techniques ranging from biotechnology to material science and nanotechnology. The result is a huge amount of data. To maintain and keep updated, this would not be an easy task. New advances in computers and information technology help to create and organize the databases quite easy. Their contents can easily be accessed, managed and updated. A WWW interface benefits the users to search the different types of data based on the types of biomaterials, their abundance, structure and applications. This provides the scope and archive of information on this emerging field of biomaterials to the global scientific community. The database is freely accessible through http://dbbiomat.iitkgp.ernet.in.
{"title":"Biomat _dBase: A Database on Biomaterials","authors":"Bano Subia, Sunandan Mukherjee, R. Bahadur, V. Correlo, L. ReisRui, R. Sabarinathan, K. Sekar, S. Kundu","doi":"10.2174/1875043501205010059","DOIUrl":"https://doi.org/10.2174/1875043501205010059","url":null,"abstract":"Biomaterial science provides a platform for the development of bio-artificial implants. Growth or development of engineered tissues for the purpose of repairing, restoring and enhancing the function of a damaged tissue or organ needs designed biomaterials. The most studied tissue engineering strategy consists on using cells growth factors and temporary three-dimensional (3D) porous scaffolds. 3D scaffolds play a very important role in the success of tissue engineering and regenerative medicine. They provide structural support for cells to proliferate and maintain their differentiated phenotype and permit the convenient delivery of cells into the patients. Several features of scaffold can influence the cell growth and its functions. The artificial extracellular matrices can be produced from different biomaterials including ceramics, natural or synthetic polymers and composites. Recent discoveries and innovations in this emerging field adopt varieties of techniques ranging from biotechnology to material science and nanotechnology. The result is a huge amount of data. To maintain and keep updated, this would not be an easy task. New advances in computers and information technology help to create and organize the databases quite easy. Their contents can easily be accessed, managed and updated. A WWW interface benefits the users to search the different types of data based on the types of biomaterials, their abundance, structure and applications. This provides the scope and archive of information on this emerging field of biomaterials to the global scientific community. The database is freely accessible through http://dbbiomat.iitkgp.ernet.in.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"59-67"},"PeriodicalIF":0.0,"publicationDate":"2012-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68110057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-11-16DOI: 10.2174/1875043501205010050
G. Rocca, S. Corrao, M. Iacono, T. Corsello, F. Farina, R. Anzalone, A. Umana
Mesenchymal (stromal) stem cells (MSC) are a broad class of stromal populations which are able to differentiate towards mature cell types, and do express molecules involved in immune modulation, tolerance induction and inflammation dampening. MSC can be virtually isolated from each adult organ, as well as from foetus-associated perinatal tissues. In particular, Wharton's jelly-derived MSC (WJ-MSC) bear all of these key properties, together with their ease of sourcing and lack of ethical issues. Cellular therapy is a key technique in regenerative medicine approaches, in particular for the treatment of diseases in which physiological processes of cellular repopulation are blocked by the underlying pathological conditions. Recent data enlightened the ability of administered cells to act also in a repopulation-independent fashion in target organs, since their peculiar immunomodulatory and anti-inflammatory features may favor organ self-repair by reactivating local progenitors by both cell-mediated or paracrine mechanisms. Translating classical regenerative medicine to "reparative medicine" or "support medicine" should represent a further therapeutic strategy independent from the differentiation capacity of MSC populations. Recent data further highlighted that WJ-MSC outperform BM-MSC (which are now being applied clinically) both in terms of immune modulation and lack of tumorigenesis (or tumor-promoting activities) in vivo. Starting from these premises, this paper analyzes the recent data on the biology of WJ-MSC, considering the role of both naive and differentiated cells in immune modulation. In particular, the role of tolerance promoting pathways via non-classical B7 costimulators or class Ib MHC molecules are examined. In addition, we also analyzed the interconnections with other mechanicistic pathways (as those driven by matrix degrading metalloproteinases) in immune modulation. Our observations strongly support the notion that WJ-MSC may constitute a new tool in regenerative and reparative medicine applications.
{"title":"Novel immunomodulatory markers expressed by human WJ-MSC: An updated review in regenerative and reparative medicine","authors":"G. Rocca, S. Corrao, M. Iacono, T. Corsello, F. Farina, R. Anzalone, A. Umana","doi":"10.2174/1875043501205010050","DOIUrl":"https://doi.org/10.2174/1875043501205010050","url":null,"abstract":"Mesenchymal (stromal) stem cells (MSC) are a broad class of stromal populations which are able to differentiate towards mature cell types, and do express molecules involved in immune modulation, tolerance induction and inflammation dampening. MSC can be virtually isolated from each adult organ, as well as from foetus-associated perinatal tissues. In particular, Wharton's jelly-derived MSC (WJ-MSC) bear all of these key properties, together with their ease of sourcing and lack of ethical issues. Cellular therapy is a key technique in regenerative medicine approaches, in particular for the treatment of diseases in which physiological processes of cellular repopulation are blocked by the underlying pathological conditions. Recent data enlightened the ability of administered cells to act also in a repopulation-independent fashion in target organs, since their peculiar immunomodulatory and anti-inflammatory features may favor organ self-repair by reactivating local progenitors by both cell-mediated or paracrine mechanisms. Translating classical regenerative medicine to \"reparative medicine\" or \"support medicine\" should represent a further therapeutic strategy independent from the differentiation capacity of MSC populations. Recent data further highlighted that WJ-MSC outperform BM-MSC (which are now being applied clinically) both in terms of immune modulation and lack of tumorigenesis (or tumor-promoting activities) in vivo. Starting from these premises, this paper analyzes the recent data on the biology of WJ-MSC, considering the role of both naive and differentiated cells in immune modulation. In particular, the role of tolerance promoting pathways via non-classical B7 costimulators or class Ib MHC molecules are examined. In addition, we also analyzed the interconnections with other mechanicistic pathways (as those driven by matrix degrading metalloproteinases) in immune modulation. Our observations strongly support the notion that WJ-MSC may constitute a new tool in regenerative and reparative medicine applications.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"50-58"},"PeriodicalIF":0.0,"publicationDate":"2012-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-06-01DOI: 10.2174/1875043501205010043
D. Kuraitis, Z. Arzhangi, A. Hyatt, B. Vulesevic, Kimberley Merrett, Jin Zhang, E. Suuronen, M. Griffith
Diseases that restrict the flow of blood to muscles in the peripheral limbs or the heart remain prevalent causes of reduced quality of life and death in developed countries. Signaling molecules that play a role in the regenerative responses are currently being exploited as potential therapies to restore blood flow and tissue function. Fibroblast growth factor-2 (FGF-2) is a potent stimulator of neovascularization. It is believed that a controlled release of a delivered cytokine is superior to a bolus administration for achieving the desired regenerative effect. Therefore, we incorporated FGF-2-containing microspheres into a hydrogel and further encased this hydrogel into a collagen capsule for implantation. Cytokine release was controlled and constant over a month-long study period, and FGF-2 released from this tertiary encapsulation system maintained its bioactivity, as measured by its proliferative effects on endothelium. In a subcutaneous mouse model, FGF-2 treatment induced a systemic response that included increased stem cell chemoattractant cytokines, the mobilization of a potent CXCR4 + angiogenic population, and also an increase in the density of small diameter blood vessels. These observations were accompanied by no changes in the systemic levels of inflammatory cytokines. Overall, tertiary encapsulation of FGF-2 retards its release and allows for a more controlled and constant delivery of FGF-2, while maintaining its bioactive effects on endothelial cells and systemic responses in vivo.
{"title":"Tertiary Biomaterial Encapsulation Controls the Release of FGF-2 without Impacting Bioactivity","authors":"D. Kuraitis, Z. Arzhangi, A. Hyatt, B. Vulesevic, Kimberley Merrett, Jin Zhang, E. Suuronen, M. Griffith","doi":"10.2174/1875043501205010043","DOIUrl":"https://doi.org/10.2174/1875043501205010043","url":null,"abstract":"Diseases that restrict the flow of blood to muscles in the peripheral limbs or the heart remain prevalent causes of reduced quality of life and death in developed countries. Signaling molecules that play a role in the regenerative responses are currently being exploited as potential therapies to restore blood flow and tissue function. Fibroblast growth factor-2 (FGF-2) is a potent stimulator of neovascularization. It is believed that a controlled release of a delivered cytokine is superior to a bolus administration for achieving the desired regenerative effect. Therefore, we incorporated FGF-2-containing microspheres into a hydrogel and further encased this hydrogel into a collagen capsule for implantation. Cytokine release was controlled and constant over a month-long study period, and FGF-2 released from this tertiary encapsulation system maintained its bioactivity, as measured by its proliferative effects on endothelium. In a subcutaneous mouse model, FGF-2 treatment induced a systemic response that included increased stem cell chemoattractant cytokines, the mobilization of a potent CXCR4 + angiogenic population, and also an increase in the density of small diameter blood vessels. These observations were accompanied by no changes in the systemic levels of inflammatory cytokines. Overall, tertiary encapsulation of FGF-2 retards its release and allows for a more controlled and constant delivery of FGF-2, while maintaining its bioactive effects on endothelial cells and systemic responses in vivo.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"43-49"},"PeriodicalIF":0.0,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68109710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-05-18DOI: 10.2174/1875043501205010035
L. Fjord-Larsen, P. Kusk, M. Torp, J. Sørensen, K. S. Ettrup, C. Bjarkam, J. Tornoe, B. Juliusson, L. Wahlberg
Nerve Growth Factor (NGF) has therapeutic effects on the cholinergic neurodegeneration in Alzheimer's disease (AD). We have previously described an implantable Encapsulated Cell Biodelivery™ device, NsG0202, capable of local delivery of NGF to the human cholinergic basal forebrain. Results from a small Phase 1b clinical study showed that the NGF dose could advantageously be increased. We have therefore developed a second generation clinical device named NsG0202.1, containing an RPE cell line (NGC0211) generated with transposon expression technology for high- dose NGF production. Furthermore, to promote cell attachment and long-term viability of NGC0211, a polyethylene terephthalate (PET) yarn scaffolding was used. The safety was tested in Gottingen minipigs during a six months period with NsG0202.1 implants placed in the basal forebrain. The devices were well tolerated and the NGC0211 viability and NGF secretion remained after 6 months in vivo. The NGF induced relevant biological responses in the surrounding cholinergic target neurons.
{"title":"Encapsulated Cell Biodelivery of Transposon-Mediated High-Dose NGF to the Göttingen Mini Pig Basal Forebrain","authors":"L. Fjord-Larsen, P. Kusk, M. Torp, J. Sørensen, K. S. Ettrup, C. Bjarkam, J. Tornoe, B. Juliusson, L. Wahlberg","doi":"10.2174/1875043501205010035","DOIUrl":"https://doi.org/10.2174/1875043501205010035","url":null,"abstract":"Nerve Growth Factor (NGF) has therapeutic effects on the cholinergic neurodegeneration in Alzheimer's disease (AD). We have previously described an implantable Encapsulated Cell Biodelivery™ device, NsG0202, capable of local delivery of NGF to the human cholinergic basal forebrain. Results from a small Phase 1b clinical study showed that the NGF dose could advantageously be increased. We have therefore developed a second generation clinical device named NsG0202.1, containing an RPE cell line (NGC0211) generated with transposon expression technology for high- dose NGF production. Furthermore, to promote cell attachment and long-term viability of NGC0211, a polyethylene terephthalate (PET) yarn scaffolding was used. The safety was tested in Gottingen minipigs during a six months period with NsG0202.1 implants placed in the basal forebrain. The devices were well tolerated and the NGC0211 viability and NGF secretion remained after 6 months in vivo. The NGF induced relevant biological responses in the surrounding cholinergic target neurons.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2012-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68108877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-04-27DOI: 10.2174/1875043501205010025
L. Carvalho, N. Breyner, R. C. Hell, P. Valério, Silviene Novikoff, A. Goes
Cell-based tissue engineering using scaffolds provides a promising option for the repair of bone tissue damage caused by trauma or aging-related degeneration such as osteoporosis. In this study, a porous 3D scaffold was used to support the differentiation process of rat adipose -derived stem cells (ADSCs) into osteoblasts in vitro. The scaffold was made with chitosan, gelatin and chondroitin. In addition, the scaffold was crosslinked by glutaraldehyide. The osteogenic differentiation of ADSCs was improved in 3D culture as shown by the cell viability assay (MTT) and analyses of, alkaline phosphatase activity (ALP), and collagen production during three weeks of culturing. During the 2nd and 3rd weeks of culturing, bone markers, such as osteopontin and osteocalcin, were detected by the PCR analysis. In vivo biocompatibility was evaluated subcutaneously in rats. A mild inflammatory response was observed during the 5 weeks. Reduction of the matrix fibers by reabsorptive cells and formation of new blood vessels were observed during this period. However, no inflammation was observed. Five weeks after the implants were placed in the calvaria -defects, a small amount of bone repair was observed. In addition, immunohistochemistry revealed the presence of EGFPs ADSCs in the newly formed extracellular matrix. These findings indicated that the chitosan-gelatin-chondroitin 3D structure enhances cellular proliferation, which may be useful in the development of biomaterials for the stimulation of adult stem cells in bone tissue engineering.
{"title":"Healing Pattern in Calvarial Bone Defects Following Bone Regeneration in Rats Guided by Chitosan Scaffold and Adipose Tissue-Derived Mesenchymal Stem Cells","authors":"L. Carvalho, N. Breyner, R. C. Hell, P. Valério, Silviene Novikoff, A. Goes","doi":"10.2174/1875043501205010025","DOIUrl":"https://doi.org/10.2174/1875043501205010025","url":null,"abstract":"Cell-based tissue engineering using scaffolds provides a promising option for the repair of bone tissue damage caused by trauma or aging-related degeneration such as osteoporosis. In this study, a porous 3D scaffold was used to support the differentiation process of rat adipose -derived stem cells (ADSCs) into osteoblasts in vitro. The scaffold was made with chitosan, gelatin and chondroitin. In addition, the scaffold was crosslinked by glutaraldehyide. The osteogenic differentiation of ADSCs was improved in 3D culture as shown by the cell viability assay (MTT) and analyses of, alkaline phosphatase activity (ALP), and collagen production during three weeks of culturing. During the 2nd and 3rd weeks of culturing, bone markers, such as osteopontin and osteocalcin, were detected by the PCR analysis. In vivo biocompatibility was evaluated subcutaneously in rats. A mild inflammatory response was observed during the 5 weeks. Reduction of the matrix fibers by reabsorptive cells and formation of new blood vessels were observed during this period. However, no inflammation was observed. Five weeks after the implants were placed in the calvaria -defects, a small amount of bone repair was observed. In addition, immunohistochemistry revealed the presence of EGFPs ADSCs in the newly formed extracellular matrix. These findings indicated that the chitosan-gelatin-chondroitin 3D structure enhances cellular proliferation, which may be useful in the development of biomaterials for the stimulation of adult stem cells in bone tissue engineering.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"25-34"},"PeriodicalIF":0.0,"publicationDate":"2012-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68108833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2012-04-19DOI: 10.2174/1875043501205010017
M. C. Collins, J. Moore, Brian J. Burrows, A. Kypson, B. Muller-Borer
Background: Human mesenchymal stem cells (hMSCs) show potential for therapeutic cellular cardiomyo- plasty. However, a range of delivery methods, including direct intramyocardial injection, have resulted in poor engraftment in vivo. We used the in vivo rat heart model to study hMSC engraftment and retention in a normal beating heart. Materials and Methods: HMSCs transfected with green fluorescent protein were injected into the left ventricle (LV) of immunocompetent rats. Hearts were cryopreserved 30 minutes (Group A), 24 hours (Group B), and 5 days (Group C) post hMSC delivery. HMSC retention was estimated using confocal fluorescence microscopy and immunohistochemistry. Measured values were compared to projected GFP-positive cellular volumes. Immunohistochemical analyses probed for the presence of human cells with human prolyl 4-hydroxylase beta (p4hβ) and an immune response with murine monocyte/macrophage antigen (CD68). Results: HMSC retention decreased significantly from 30 minutes to 5 days (p<0.05). In Group A the projected GFP positive cellular volume of 31% correlated with measured values and was significantly greater than the 1% predicted cellular volume in Group C. Moreover, human p4hβ was detected in Groups A and B, and not in Group C. Conversely, CD68 was detected in Groups B and C and not in Group A. Conclusions: In immunocompetent rats, engraftment and retention of hMSCs delivered intramyocardially significantly declines over a five day period. The influx of monocytes/macrophages suggests an unfavorable micro-environment for exogenous stem cell survival, confirmed by the absence of human cells detected five days post injection.
{"title":"Early Cell Loss Associated with Mesenchymal Stem Cell Cardiomyoplasty","authors":"M. C. Collins, J. Moore, Brian J. Burrows, A. Kypson, B. Muller-Borer","doi":"10.2174/1875043501205010017","DOIUrl":"https://doi.org/10.2174/1875043501205010017","url":null,"abstract":"Background: Human mesenchymal stem cells (hMSCs) show potential for therapeutic cellular cardiomyo- plasty. However, a range of delivery methods, including direct intramyocardial injection, have resulted in poor engraftment in vivo. We used the in vivo rat heart model to study hMSC engraftment and retention in a normal beating heart. Materials and Methods: HMSCs transfected with green fluorescent protein were injected into the left ventricle (LV) of immunocompetent rats. Hearts were cryopreserved 30 minutes (Group A), 24 hours (Group B), and 5 days (Group C) post hMSC delivery. HMSC retention was estimated using confocal fluorescence microscopy and immunohistochemistry. Measured values were compared to projected GFP-positive cellular volumes. Immunohistochemical analyses probed for the presence of human cells with human prolyl 4-hydroxylase beta (p4hβ) and an immune response with murine monocyte/macrophage antigen (CD68). Results: HMSC retention decreased significantly from 30 minutes to 5 days (p<0.05). In Group A the projected GFP positive cellular volume of 31% correlated with measured values and was significantly greater than the 1% predicted cellular volume in Group C. Moreover, human p4hβ was detected in Groups A and B, and not in Group C. Conversely, CD68 was detected in Groups B and C and not in Group A. Conclusions: In immunocompetent rats, engraftment and retention of hMSCs delivered intramyocardially significantly declines over a five day period. The influx of monocytes/macrophages suggests an unfavorable micro-environment for exogenous stem cell survival, confirmed by the absence of human cells detected five days post injection.","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"151 1","pages":"17-24"},"PeriodicalIF":0.0,"publicationDate":"2012-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68108819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: To construct tissue-engineered (TE) venous valves in vitro using two types of bone marrow-derived progenitor cells and decellularized scaffold. Methods: Bone marrow-derived multipotent adult progenitor cells (MAPC) and endothelial progenitor cells (EPC) from canines were labeled by Hoechst or PKH26, respectively. And they were both implanted into an allograft acellular vein containing a valve to construct a tissue-engineered venous valve in vitro by culturing in the medium. Growth and migration of MAPC and EPC in the scaffold and inner surface were observed via cryosectioning. The cells distribution, differentiation and endothelium in the scaffold material were assessed by HE staining and immunohistochemical staining. Result: MAPC grew, migrated, and differentiated into smooth muscle-like cells in the scaffold material. EPC grew, migrated, and differentiated into the endothelial cells; and they completely endothelialized the inner surface of the vascular and both sides of the venous valves. Conclusion: We successfully constructed tissue-engineered vein valves using two types of bone marrow-derived progenitor cells and decellularized
{"title":"Construction of Tissue-Engineered Venous Valves in Vitro Using TwoTypes of Progenitor Cells and Decellularized Scaffolds Category: OriginalArticle","authors":"Yu Wen, Jian‐ming Yuan, R. Dang, Xiang-Qun Yang, Shao‐hu Xiong, Man-Ru Shen, Yong‐zhen Zhang, Chuan‐sen Zhang","doi":"10.2174/1875043501205010009","DOIUrl":"https://doi.org/10.2174/1875043501205010009","url":null,"abstract":"Objective: To construct tissue-engineered (TE) venous valves in vitro using two types of bone marrow-derived progenitor cells and decellularized scaffold. Methods: Bone marrow-derived multipotent adult progenitor cells (MAPC) and endothelial progenitor cells (EPC) from canines were labeled by Hoechst or PKH26, respectively. And they were both implanted into an allograft acellular vein containing a valve to construct a tissue-engineered venous valve in vitro by culturing in the medium. Growth and migration of MAPC and EPC in the scaffold and inner surface were observed via cryosectioning. The cells distribution, differentiation and endothelium in the scaffold material were assessed by HE staining and immunohistochemical staining. Result: MAPC grew, migrated, and differentiated into smooth muscle-like cells in the scaffold material. EPC grew, migrated, and differentiated into the endothelial cells; and they completely endothelialized the inner surface of the vascular and both sides of the venous valves. Conclusion: We successfully constructed tissue-engineered vein valves using two types of bone marrow-derived progenitor cells and decellularized","PeriodicalId":88761,"journal":{"name":"The open tissue engineering and regenerative medicine journal","volume":"5 1","pages":"9-16"},"PeriodicalIF":0.0,"publicationDate":"2012-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68108739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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