The incorporation of vasculature is known to be effective in tissue or organ functional regeneration.However,a vague understanding of the interaction between epidermal appendages and their vascular niches is a foremos...The incorporation of vasculature is known to be effective in tissue or organ functional regeneration.However,a vague understanding of the interaction between epidermal appendages and their vascular niches is a foremost obstacle to obtaining sweat gland(SG)-specific vasculature units.Here,we map their precise anatomical con-nections and report that the interplay between SG cells(SGCs)and the surrounding vascular niche is key for glandular development and homeostasis maintenance.To replicate this interplay in vitro,we used three-dimensional(3D)bioprinting to generate reproducible SGC spheroids from differentiated adipose-derived mesenchymal stem cells(ADSCs).With dermal microvascular endothelial cells(DMECs),sacrificial templates made from poly(ε-caprolactone)(PCL)were fabricated to pattern the vascular niche.This interplay model promoted physiologically relevant vascularized glandular morphogenesis in vitro and in vivo.We identified a reciprocal regulatory mechanism for promoting SGs regeneration via contact-independent cell communication and direct cell-cell interactions between SGs and the vasculature.We envision the successful use of our approach for vascularized organ regeneration in the near future.展开更多
Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the...Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.展开更多
Even with many advances in design strategies over the past three decades,an enormous gap remains between existing tissue engineering skin and natural skin.Currently available in vitro skin models still cannot replicat...Even with many advances in design strategies over the past three decades,an enormous gap remains between existing tissue engineering skin and natural skin.Currently available in vitro skin models still cannot replicate the three-dimensionality and heterogeneity of the dermal microenvironment sufficiently to recapitulate many of the known characteristics of skin disorder or disease in vivo.Three-dimensional(3D)bioprinting enables precise control over multiple compositions,spatial distributions and architectural complexity,therefore offering hope for filling the gap of structure and function between natural and artificial skin.Our understanding of wound healing process and skin disease would thus be boosted by the development of in vitro models that could more completely capture the heterogeneous features of skin biology.Here,we provide an overview of recent advances in 3D skin bioprinting,as well as design concepts of cells and bioinks suitable for the bioprinting process.We focus on the applications of this technology for engineering physiological or pathological skin model,focusing more specifically on the function of skin appendages and vasculature.We conclude with current challenges and the technical perspective for further development of 3D skin bioprinting.展开更多
基金National Natural Science Foundation of China(81830064,81721092,32000969,82002056)Key Support Program for Growth Factor Research(SZYZ-TR-03)+3 种基金Chinese PLA General Hospital for Military Medical Innovation Research Project(CX-19026)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)Military Medical Research and Development Projects(AWS17J005)Beijing Natural Science Foundation(7204306).
文摘The incorporation of vasculature is known to be effective in tissue or organ functional regeneration.However,a vague understanding of the interaction between epidermal appendages and their vascular niches is a foremost obstacle to obtaining sweat gland(SG)-specific vasculature units.Here,we map their precise anatomical con-nections and report that the interplay between SG cells(SGCs)and the surrounding vascular niche is key for glandular development and homeostasis maintenance.To replicate this interplay in vitro,we used three-dimensional(3D)bioprinting to generate reproducible SGC spheroids from differentiated adipose-derived mesenchymal stem cells(ADSCs).With dermal microvascular endothelial cells(DMECs),sacrificial templates made from poly(ε-caprolactone)(PCL)were fabricated to pattern the vascular niche.This interplay model promoted physiologically relevant vascularized glandular morphogenesis in vitro and in vivo.We identified a reciprocal regulatory mechanism for promoting SGs regeneration via contact-independent cell communication and direct cell-cell interactions between SGs and the vasculature.We envision the successful use of our approach for vascularized organ regeneration in the near future.
基金supported by grants from the National Natural Science Foundation of China(81830064,81721092,32000969,82002056)Key Support Program for Growth Factor Research(SZYZ-TR-03)+3 种基金Chinese PLA General Hospital for Military Medical Innovation Research Project(CX-19026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005)Beijing Natural Science Foundation(7204306).
文摘Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.
基金supported by the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)Key Basic Research Projects of the Foundation Strengthening Plan(2022-JCJQ-ZD-096-00)+2 种基金National Key Research and Development Program of China(2022YFA1104604)National Natural Science Foundation of China(32000969)Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Even with many advances in design strategies over the past three decades,an enormous gap remains between existing tissue engineering skin and natural skin.Currently available in vitro skin models still cannot replicate the three-dimensionality and heterogeneity of the dermal microenvironment sufficiently to recapitulate many of the known characteristics of skin disorder or disease in vivo.Three-dimensional(3D)bioprinting enables precise control over multiple compositions,spatial distributions and architectural complexity,therefore offering hope for filling the gap of structure and function between natural and artificial skin.Our understanding of wound healing process and skin disease would thus be boosted by the development of in vitro models that could more completely capture the heterogeneous features of skin biology.Here,we provide an overview of recent advances in 3D skin bioprinting,as well as design concepts of cells and bioinks suitable for the bioprinting process.We focus on the applications of this technology for engineering physiological or pathological skin model,focusing more specifically on the function of skin appendages and vasculature.We conclude with current challenges and the technical perspective for further development of 3D skin bioprinting.
