1.Research advances on mesenchymal stem cells and their derivatives in the treatment of acne scars.
Fang LI ; Yuan CAI ; Cheng Liang DENG
Chinese Journal of Burns 2022;38(6):595-600
Acne is a common chronic inflammatory disease of the skin that often occurs on the face, and acne scars are often secondary to the healing process of acne, which often leads to impaired appearance and psychological disorders of patients. The current treatment for acne scars is extremely difficult. With the development of regenerative medicine, stem cell transplantation has become a new treatment for acne scars. In recent years, it has been reported that stem cells and their derivatives can effectively antagonize the formation of acne scars. Therefore, this paper briefly reviews the basic and clinical researches on the treatment of acne scars with various mesenchymal stem cells and their derivatives, aiming to provide theoretical basis and reference for the stem cell therapy of acne scars.
Acne Vulgaris/pathology*
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Cicatrix/pathology*
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Humans
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Mesenchymal Stem Cells
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Skin/pathology*
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Stem Cell Transplantation
2.Effect of mesenchymal stem cell transplantation on immunological injury of the ovary in mice.
Wei-na LI ; Guangzhou 510632, CHINA. ; Qi-xuan XIE ; Jun-wen QIN ; Wei HUANG ; Shao-en YE ; Feng LUO ; Chun-xue ZHANG ; Luan-juan XIAO
Journal of Southern Medical University 2011;31(5):825-829
OBJECTIVETo investigate the effect of mesenchymal stem cell (MSC) transplantation in repairing ovarian injury in mice sensitized with porcine ovarian proteins.
METHODSWild-type female mice with ICR background (6-8 weeks old) were divided randomly into groups A, B and C (n=12). In groups B and C, the mice were treated with the total protein extract from porcine ovary to induce immunological injury of the ovary, while those in group A received no treatment. MSCs-derived from GFP transgenic mice were transplanted into the mice of group C, and equal volume of PBS was injected intraperitoneally in mice of the other two groups. PCR was used to detect GFP gene in the genomic DNA of the ovaries to assess MSCs homing in the ovary, and the reparative effect of MSCs on ovarian injury was evaluated using HE staining and TUNEL analysis.
RESULTSAfter transplantation, the MSCs could reach the injured ovaries to promote the repair of the ovarian injury, resulting also in reduced apoptosis of the granulosa cells (GCs) in the injured ovaries.
CONCLUSIONMSCs transplantation can promote the recovery of the immunological injury of the ovary in mice, the mechanism of which may involve reduced apoptosis of the GCs.
Animals ; Apoptosis ; Bone Marrow Cells ; Female ; Granulosa Cells ; cytology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; Mice ; Mice, Inbred ICR ; Ovarian Diseases ; pathology ; surgery ; Ovary ; cytology ; pathology
3.The differences between adipose tissue derived stem cells and lipoma mesenchymal stem cells in characteristics.
Yi-wei QIAN ; Jian-hua GAO ; Feng LU ; Xu-dong ZHENG
Chinese Journal of Plastic Surgery 2010;26(2):125-132
OBJECTIVETo compared the biological characteristics of adipose-derived stem cells and lipoma-derived mesenchymal stem cells (LMSCs) in vitro, so as to assess the safety of adipose-derived stem cells( ASCs) for transplantation.
METHODSRegular slice and stain of adipose and lipoma tissue were performed. ASCs and LMSCs were isolation from the two tissues by enzymatic digestion, and the appearance of the cultured cells was observed. The cell viability was evaluated with MTS chromatometry and cell growth curve was generated. Flow cytometry was performed for cell cycle analysis and the expression of the cell surface marker profiles. QRT-PCR was used to detect the expression of tumor-specific gene (the high-mobility group AT-hook 2, HMGA2), and immunocytochemistry was used to detect the expression of telomerase.
RESULTSMarked difference was observed in histologic sections of adipose tissue and lipoma tissue. ASCs showed a good consistent in cell morphology while LMSCs not. ASCs showed a significant lower proliferation capacity than LMSCs by MTS chromatometry (P = 0.000). The expression of CD29, CD44, CD105 was similar in ASCs and LMSCs, while the level of CD133 was significantly lower in ASCs (5.35%) than in LMSCs (26.87%). The expression of HMGA2 was lower in ASCs (RQ = 1) than in LMSCs (RQ = 1.79) by qRT-PCR, it has statistically difference between them (P < 0.01); And in ASCs and LMSCs, the integrated optical intensity (IA) values of hTERT expression are 1379.597 +/- 498.617 and 3 328.108 +/- 902.856, size (area) are 132,390.27 +/- 35,568.945 and 238,000.53 +/- 49,264.289, density (mean) are 0.009 +/- 0.003 and 0.014 +/- 0.003, revealed the expression of hTERT also shown a significant lower level in ASCs than in LMSCs by immunocytochemistry.
CONCLUSIONSIt indicates significant difference between ASCs and LMSCs in the biological characteristics in vitro. There is no evidence of malignant transformation of ASCs.
Adipose Tissue ; cytology ; Adult ; Cells, Cultured ; Humans ; Lipoma ; pathology ; Male ; Mesenchymal Stromal Cells ; cytology ; Stem Cells ; cytology
4.Epithelial mesenchymal transition in prostate cancer: Advances in current research.
Bin YAN ; Ning JIANG ; Yuan-jie NIU
National Journal of Andrology 2015;21(9):847-851
Epithelial mesenchymal transition (EMT) is a process of normal cell physiological development, in which epithelial cells transform into mesenchyme cells through a specific program. EMT plays a key role in inflammatory reaction, cell development, tumor invasion, and metastasis and has an interrelation with prostate cancer stem cells. Recent researches show the involvement of EMT in the development and metastasis of prostate cancer. This article reviews the specific roles and action mechanisms of EMT in the progression of prostate cancer.
Biomedical Research
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Cell Differentiation
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Disease Progression
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Epithelial Cells
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physiology
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Epithelial-Mesenchymal Transition
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physiology
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Humans
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Male
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Mesenchymal Stromal Cells
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Neoplastic Stem Cells
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physiology
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Prostatic Neoplasms
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pathology
5.Tumor associated stem/progenitor cells in tumorigenesis and progression of cancer.
Chinese Journal of Pathology 2011;40(3):145-146
Animals
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Cell Proliferation
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Disease Progression
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Endothelial Cells
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pathology
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Humans
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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metabolism
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Mesenchymal Stromal Cells
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immunology
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metabolism
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pathology
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Neoplasms
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immunology
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pathology
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Neoplastic Stem Cells
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pathology
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Neovascularization, Pathologic
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pathology
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Stem Cells
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pathology
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T-Lymphocytes
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immunology
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pathology
6.Intramarrow injection of beta-catenin-activated, but not naive mesenchymal stromal cells stimulates self-renewal of hematopoietic stem cells in bone marrow.
Ji Yeon AHN ; Gyeongsin PARK ; Jae Seung SHIM ; Jong Wook LEE ; Il Hoan OH
Experimental & Molecular Medicine 2010;42(2):122-131
Bone marrow mesenchymal stromal cells (MSCs) have been implicated in the microenvironmental support of hematopoietic stem cells (HSCs) and often co-transplanted with HSCs to facilitate recovery of ablated bone marrows. However, the precise effect of transplanted MSCs on HSC regeneration remains unclear because the kinetics of HSC self-renewal in vivo after co-transplantation has not been monitored. In this study, we examined the effects of intrafemoral injection of MSCs on HSC self-renewal in rigorous competitive repopulating unit (CRU) assays using congenic transplantation models in which stromal progenitors (CFU-F) were ablated by irradiation. Interestingly, naive MSCs injected into femur contributed to the reconstitution of a stromal niche in the ablated bone marrows, but did not exert a stimulatory effect on the in-vivo self-renewal of co-transplanted HSCs regardless of the transplantation methods. In contrast, HSC self-renewal was four-fold higher in bone marrows intrafemorally injected with beta-catenin-activated MSCs. These results reveal that naive MSCs lack a stimulatory effect on HSC self-renewal in-vivo and that stroma must be activated during recoveries of bone marrows. Stromal targeting of wnt/beta-catenin signals may be a strategy to activate such a stem cell niche for efficient regeneration of bone marrow HSCs.
Animals
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Bone Marrow/metabolism/pathology
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Hematopoietic Stem Cell Mobilization
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*Hematopoietic Stem Cell Transplantation
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Hematopoietic Stem Cells/pathology
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Mesenchymal Stem Cell Transplantation
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Mesenchymal Stem Cells/*metabolism/pathology
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Mice
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Mice, Inbred C57BL
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Radiation Chimera
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Regeneration
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Stem Cell Niche/metabolism/pathology
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Stromal Cells/*metabolism/pathology
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*Transplantation Conditioning
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beta Catenin/*metabolism
7.Effects of exosomes from human adipose-derived mesenchymal stem cells on pulmonary vascular endothelial cells injury in septic mice and its mechanism.
Wei Xia CAI ; Kuo SHEN ; Tao CAO ; Jing WANG ; Ming ZHAO ; Ke Jia WANG ; Yue ZHANG ; Jun Tao HAN ; Da Hai HU ; Ke TAO
Chinese Journal of Burns 2022;38(3):266-275
Objective: To investigate the effects of exosomes from human adipose-derived mesenchymal stem cells (ADSCs) on pulmonary vascular endothelial cells (PMVECs) injury in septic mice and its mechanism. Methods: The experimental research method was adopted. The primary ADSCs were isolated and cultured from the discarded fresh adipose tissue of 3 patients (female, 10-25 years old), who were admitted to the First Affiliated Hospital of Air Force Medical University undergoing abdominal surgery, and the cell morphology was observed by inverted phase contrast microscope on the 5th day. The expressions of CD29, CD34, CD44, CD45, CD73, and CD90 of ADSCs in the third passage were detected by flow cytometry. The third to the fifth passage of ADSCs were collected, and their exosomes from the cell supernatant were obtained by differential ultracentrifugation, and the shape, particle size, and the protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and β-actin of exosomes were detected, respectively, by transmission electron microscopy, nano-particle tracking analysis and Western blotting. Twenty-four adult male BALB/c mice were adopted and were divided into normal control group, caecal ligation perforation (CLP) alone group, and CLP+ADSC-exosome group with each group of 8 according to random number table (the same grouping method below) and were treated accordingly. At 24 h after operation, tumor necrosis factor (TNF-α) and interleukin 1β (IL-1β) levels of mice serum were detected by enzyme-linked immunosorbent assay, and lung tissue morphology of mice was detected by hematoxylin-eosin and myeloperoxidase staining, and the expression of 8-hydroxy-deoxyguanosine (8-OHdG) of mouse lung cells was detected by immunofluorescence method. Primary PMVECs were obtained from 1-month-old C57 mice regardless gender by tissue block method. The expression of CD31 of PMVECs was detected by immunofluorescence and flow cytometry. The third passage of PMVECs was co-cultured with ADSCs derived exosomes for 12 h, and the phagocytosis of exosomes by PMVECs was detected by PKH26 kit. The third passage of PMVECs were adopted and were divided into blank control group, macrophage supernatant alone group, and macrophage supernatant+ADSC-exosome group, with 3 wells in each group, which were treated accordingly. After 24 h, the content of reactive oxygen species in cells was detected by flow cytometry, the expression of 8-OHdG in cells was detected by immunofluorescence, and Transwell assay was used to determine the permeability of cell monolayer. The number of samples in above were all 3. Data were statistically analyzed with one-way analysis of variance and least significant difference t test. Results: The primary ADSCs were isolated and cultured to day 5, growing densely in a spindle shape with a typical swirl-like. The percentages of CD29, CD44, CD73 and CD90 positive cells of ADSCs in the third passage were all >90%, and the percentages of CD34 and CD45 positive cells were <5%. Exosomes derived from ADSCs of the third to fifth passages showed a typical double-cavity disc-like structure with an average particle size of 103 nm, and the protein expressions of CD9, CD63 and TSG101 of exosomes were positive, while the protein expression of β-actin of exosomes was negative. At 24 h after operation, compared with those in normal control group, both the levels of TNF-α and IL-1β of mice serum in CLP alone group were significantly increased (with t values of 28.76 and 29.69, respectively, P<0.01); compared with those in CLP alone group, both the content of TNF-α and IL-1β of mice serum in CLP+ADSC-exosome group was significantly decreased (with t values of 9.90 and 4.76, respectively, P<0.05 or P<0.01). At 24 h after surgery, the pulmonary tissue structure of mice in normal control group was clear and complete without inflammatory cell infiltration; compared with those in normal control group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP alone group were more obvious; compared with those in CLP alone group, the pulmonary tissue edema and inflammatory cell infiltration of mice in CLP+ADSC-exosome group were significantly reduced. At 24 h after operation, endothelial cells in lung tissues of mice in 3 groups showed positive expression of CD31; compared with that in normal control group, the fluorescence intensity of 8-OHdG positive cells of the lung tissues of mice in CLP alone group was significantly increased, and compared with that in CLP alone group, the fluorescence intensity of 8-OHdG positive cells in the lung tissues of mice in CLP+ADSC-exosome group was significantly decreased. The PMVECs in the 3rd passage showed CD31 positive expression by immunofluorescence, and the result of flow cytometry showed that CD31 positive cells accounted for 99.5%. At 12 h after co-culture, ADSC-derived exosomes were successfully phagocytose by PMVECs and entered its cytoplasm. At 12 h after culture of the third passage of PMVECs, compared with that in blank control group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant alone group was significantly increased (t=15.73, P<0.01); compared with that in macrophage supernatant alone group, the fluorescence intensity of reactive oxygen species of PMVECs in macrophage supernatant+ADSC-exosome group was significantly decreased (t=4.72, P<0.01). At 12 h after culture of the third passage of PMVECs, and the 8-OHdG positive fluorescence intensity of PMVECs in macrophage supernatant alone group was significantly increased; and compared with that in blank control group, the 8-OHdG positive fluorescence intensity of PMVECs in macrophage+ADSC-exosome supernatant group was between blank control group and macrophage supernatant alone group. At 12 h after culture of the third passage PMVECs, compared with that in blank control group, the permeability of PMVECs monolayer in macrophage supernatant alone group was significantly increased (t=6.34, P<0.01); compared with that in macrophage supernatant alone group, the permeability of PMVECs monolayer cells in macrophage supernatant+ADSC-exosome group was significantly decreased (t=2.93, P<0.05). Conclusions: Exosomes derived from ADSCs can ameliorate oxidative damage in mouse lung tissue, decrease the level of reactive oxygen species, 8-OHdG expression, and permeability of PMVECs induced by macrophage supernatant.
Animals
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Endothelial Cells/metabolism*
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Exosomes/metabolism*
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Female
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Humans
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Lung Injury/metabolism*
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Male
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Mesenchymal Stem Cells/metabolism*
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Mice
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Sepsis/pathology*
8.The Latest Research Progress of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients --Review.
Xiao-Sui LING ; Hai-Ping HE ; Li-Hua ZHANG ; Fan LI
Journal of Experimental Hematology 2023;31(4):1233-1236
Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Bone marrow mesenchymal stem cells (MSC) play an important role in the progression of MM. Compared with normal donor derived MSC (ND-MSC), MM patients derived MSC (MM-MSC) exhibit abnormalities in genes, signaling pathways, protein expression levels and cytokines secreted by themselves. Moreover, the exosomes of MM-MSC can interact with the bone marrow microenvironment. The above reasons can lead to MM cell proliferation, chemoresistance, impaired osteogenic differentiation of MM-MSC, and affect the immunomodulatory capacity of MM patients. In order to further understand the pathogenesis and related influencing factors of MM, this paper reviews the latest research progress of MM-MSC.
Humans
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Multiple Myeloma/pathology*
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Osteogenesis
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Mesenchymal Stem Cells
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Cell Differentiation
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Bone Marrow/metabolism*
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Bone Marrow Cells/metabolism*
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Tumor Microenvironment
9.Progression in metastasis of colorectal carcinoma.
Journal of Zhejiang University. Medical sciences 2014;43(4):486-493
Globally, the incidence of colorectal carcinoma (CRC) ranks the third among all cancers. The incidence of CRC is continually increasing in China. Invasion and metastasis are the major causes of death. Metastasis is a complex multistep malignant process, including the detachment of tumor cells from the primary site, interaction of tumor cells with the surrounding extracellular matrix, entering into the circulation or lymph system, adhesion to the endothelial cells of vascular wall, migration of tumor cells into secondary sites, angiogenesis and formation of new metastases. This article reviews the recent research progress in aspects of the metastasis related genes, microRNAs, epithelial mesenchymal transition, tumor stem cells, and micro environment of colorectal cancer.
Colorectal Neoplasms
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pathology
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Epithelial-Mesenchymal Transition
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Humans
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MicroRNAs
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Neoplasm Invasiveness
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Neoplasm Metastasis
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genetics
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pathology
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Neoplastic Stem Cells
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Tumor Microenvironment
10.Human hair follicle-derived mesenchymal stem cells promote tendon repair in a rabbit Achilles tendinopathy model.
Yingyu MA ; Zhiwei LIN ; Xiaoyi CHEN ; Xin ZHAO ; Yi SUN ; Ji WANG ; Xiaozhou MOU ; Hai ZOU ; Jinyang CHEN
Chinese Medical Journal 2023;136(9):1089-1097
BACKGROUND:
Hair follicles are easily accessible and contain stem cells with different developmental origins, including mesenchymal stem cells (MSCs), that consequently reveal the potential of human hair follicle (hHF)-derived MSCs in repair and regeneration. However, the role of hHF-MSCs in Achilles tendinopathy (AT) remains unclear. The present study investigated the effects of hHF-MSCs on Achilles tendon repair in rabbits.
METHODS:
First, we extracted and characterized hHF-MSCs. Then, a rabbit tendinopathy model was constructed to analyze the ability of hHF-MSCs to promote repair in vivo . Anatomical observation and pathological and biomechanical analyses were performed to determine the effect of hHF-MSCs on AT, and quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunohistochemical staining were performed to explore the molecular mechanisms through which hHF-MSCs affects AT. Furthermore, statistical analyses were performed using independent sample t test, one-way analysis of variance (ANOVA), and one-way repeated measures multivariate ANOVA as appropriate.
RESULTS:
Flow cytometry, a trilineage-induced differentiation test, confirmed that hHF-derived stem cells were derived from MSCs. The effect of hHF-MSCs on AT revealed that the Achilles tendon was anatomically healthy, as well as the maximum load carried by the Achilles tendon and hydroxyproline proteomic levels were increased. Moreover, collagen I and III were upregulated in rabbit AT treated with hHF-MSCs (compared with AT group; P < 0.05). Analysis of the molecular mechanisms revealed that hHF-MSCs promoted collagen fiber regeneration, possibly through Tenascin-C (TNC) upregulation and matrix metalloproteinase (MMP)-9 downregulation.
CONCLUSIONS
hHF-MSCs can be a treatment modality to promote AT repair in rabbits by upregulating collagen I and III. Further analysis revealed that treatment of AT using hHF-MSCs promoted the regeneration of collagen fiber, possibly because of upregulation of TNC and downregulation of MMP-9, thus suggesting that hHF-MSCs are more promising for AT.
Animals
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Humans
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Rabbits
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Hair Follicle
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Achilles Tendon/pathology*
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Tendinopathy/pathology*
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Proteomics
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Collagen Type I
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Mesenchymal Stem Cells