Potential efficacy and mechanism of medicinal plants on chronic kidney disease-associated vascular calcification:a review

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients.Modern medicine relies on calcium-phosphorus binding agents,calcium mimetics,active vitamin D,and hemodialysis to prevent and treat vascular calcification,however,their efficacy is unsatisfactory and adverse reactions often occur.Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification,which can significantly improve patients’symptoms,but its specific mechanism has not been fully elucidated yet.In this paper,we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years,summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification,and explored the mechanism of action of herbal medicine,which will provide a new strategy for promoting the prevention and treatment of vascular calcification.

Chondrogenic priming of human fetal synovium-derived stem cells in an adult stem cell matrix microenvironment

Cartilage defects are a challenge to treat clinically due to the avascular nature of cartilage.Low immunogenicity and extensive proliferation and multidifferentiation potential make fetal stem cells a promising source for regenerative medicine.In this study,we aimed to determine whether fetal synovium-derived stem cells(FSDSCs)exhibited replicative senescence and whether expansion on decellularized extracellular matrix(dECM)deposited by adult SDSCs(AECM)promoted FSDSCs’chondrogenic potential.FSDSCs from passage 2 and 9 were compared for chondrogenic potential,using Alcian blue staining for sulfated glycosaminoglycans(GAGs),biochemical analysis for DNA and GAG amounts,and real-time PCR for chondrogenic genes including ACAN and COL2A1.Passage 3 FSDSCs were expanded for one passage on plastic flasks(PL),AECM,or dECM deposited by fetal SDSCs(FECM).During expansion,cell proliferation was evaluated using flow cytometry for proliferation index,stem cell surface markers,and resistance to hydrogen peroxide.During chondrogenic induction,expanded FSDSCs were evaluated for tri-lineage differentiation capacity.We found that cell expansion enhanced FSDSCs’chondrogenic potential at least up to passage 9.Expansion on dECMs promoted FSDSCs’proliferative and survival capacity and adipogenic differentiation but not osteogenic capacity.AECM-primed FSDSCs exhibited an enhanced chondrogenic potential.

Matrix from urine stem cells boosts tissue-specific stem cell mediated functional cartilage reconstruction

Articular cartilage has a limited capacity to self-heal once damaged.Tissue-specific stem cells are a solution for cartilage regeneration;however,ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration.Our previous report demonstrated that decellularized extracellular matrix(dECM)deposited by human synovium-derived stem cells(SDSCs),adipose-derived stem cells(ADSCs),urine-derived stem cells(UDSCs),or dermal fibroblasts(DFs)provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential,particularly for dECM deposited by UDSCs.To make the cell-derived dECM(C-dECM)approach applicable clinically,in this study,we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells(IPFSCs),an easily accessible alternative for SDSCs,by the abovementioned C-dECMs,in vivo application for functional cartilage repair in a rabbit osteochondral defect model,and potential cellular and molecular mechanisms underlying this rejuvenation.We found that C-dECM rejuvenation promoted rabbit IPFSCs’cartilage engineering and functional regeneration in both ex vivo and in vivo models,particularly for the dECM deposited by UDSCs,which was further confirmed by proteomics data.RNA-Seq analysis indicated that both mesenchymal-epithelial transition(MET)and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs’chondrogenic capacity,which needs further investigation.

Strategies to minimize hypertrophy in cartilage engineering and regeneration

Due to a blood supply shortage,articular cartilage has a limited capacity for selfhealing once damaged.Articular chondrocytes,cartilage progenitor cells,embryonic stem cells,and mesenchymal stem cells are candidate cells for cartilage regeneration.Significant current attention is paid to improving chondrogenic differentiation capacity;unfortunately,the potential chondrogenic hypertrophy of differentiated cells is largely overlooked.Consequently,the engineered tissue is actually a transient cartilage rather than a permanent one.The development of hypertrophic cartilage ends with the onset of endochondral bone formation which has inferior mechanical properties.In this review,current strategies for inhibition of chondrogenic hypertrophy are comprehensively summarized;the impact of cell source options is discussed;and potential mechanisms underlying these strategies are also categorized.This paper aims to provide guidelines for the prevention of hypertrophy in the regeneration of cartilage tissue.This knowledge may also facilitate the retardation of osteophytes in the treatment of osteoarthritis.

Decellularized extracellular matrix mediates tissue construction and regeneration

Contributing to organ formation and tissue regeneration,extracellular matrix(ECM)constituents provide tissue with three-dimensional(3D)structural integrity and cellular-function regulation.Containing the crucial traits of the cellular microenvironment,ECM substitutes mediate cell–matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo.However,these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures.Cultured cells also produce rich ECM,particularly stromal cells.Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well.Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select,produce,and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration.Overall,the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed.Moreover,current preclinical applications by which ECM components modulate the wound-healing process are reviewed.

Nidogen:A matrix protein with potential roles in musculoskeletal tissue regeneration

Basement membrane proteins are known to guide cell structures,differentiation,and tissue repair.Although there is a wealth of knowledge on the functions of laminins,per-lecan,and type IV collagen in maintaining tissue homeostasis,not much is known about nidogen.As a key molecule in the basement membrane,nidogen contributes to the formation of a delicate microenvironment that proves necessary for stem cell lineage-specific differentiation.In this review,the expression of nidogen is delineated at both cellular and tissue levels from embryonic to adult stages of development;the effect of nidogens is also summarized in the context of musculoskeletal development and regeneration,including but not limited to adipogenesis,angiogenesis,chondrogenesis,myogenesis,and neurogenesis.Furthermore,potential mechanisms underlying the role of nidogens in stem cell-based tissue regeneration are also discussed.This concise review is expected to facilitate our existing understanding and utilization of nidogen in tissue engineering and regeneration.