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( Sandra Villanueva ),( Fernando Gonzalez ),( Eduardo Lorca ),( Andres Tapia ),( Valentina Lopez G ),( Rocio Strodthoff ),( Francisca Fajre ),( Juan E. Carreno ),( Ricardo Valjalo ),( Cesar Vergara ) 대한신장학회 2019 Kidney Research and Clinical Practice Vol.38 No.2
Background: Chronic kidney disease (CKD) is a growing public health concern, and available treatments are insufficient in limiting disease progression. New strategies, including regenerative cell-based therapies, have emerged as therapeutic alternatives. Results from several groups, including our own, have reported evidence of a supportive role for mesenchymal stromal cells (MSCs) in functional recovery and prevention of tissue damage in murine models of CKD. Prompted by these data, an open pilot study was conducted to assess the safety and efficacy of a single injection of autologous adipose tissue-derived MSCs (AT-MSCs) for treatment of CKD. Methods: AT-MSCs were infused intravenously into six CKD patients at a dose of 1 million cells/kg. Patients were stabilized and followed for one year prior to MSC infusion and one year following infusion. Results: No patients presented with adverse effects. Statistically significant improvement in urinary protein excretion was observed in AT-MSCs transplanted patients, from a median of 0.75 g/day (range, 0.15-9.57) at baseline to 0.54 g/day (range, 0.01-2.66) at month 12 (P = 0.046). The glomerular filtration rate was not significantly decreased post-infusion of AT-MSCs. Conclusion: Findings from this pilot study demonstrate that intravenous infusion of autologous expanded AT-MSCs into CKD patients was not associated with adverse effects and could benefit patients already undergoing standard medical treatment.
( Hyo Eun Moon ),( Hyung Woo Park ),( Hye Young Shin ),( Seung Leal Paek ),( Dong Gyu Kim ),( Jin H Son ),( Sun Ha Paek ) 한국조직공학과 재생의학회 2010 조직공학과 재생의학 Vol.7 No.2
Purpose: With an approach of carrying out a transcriptome microarray analysis using early-passage adipose tissue-derived mesenchymal stromal cells from human adult patients with early-onset hereditary parkin deficient Parkinson`s disease (PD) as well as late-onset idiopathic PD, we aimed to understand brain pathology in PD patients. Methods: Here, we isolated human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) of patients with idiopathic PD and parkin deficient PD in comparison with non-PD patients and profiled their gene expression using Affymetrix cDNA microarray analysis. Human adipose tissue is a rich source of MSCs, providing an abundant and accessible source of adult stem cells. Results: The hAD-MSCs of patients with idiopathic PD were named as "PD", with parkin deficient PD as "Parkin" and with pituitary adenoma as "non-PD" shortly. Initially, Differentially Expressed Genes (DEGs, total 413 genes) were classified and summarized among non-PD, PD and Parkin. Moreover, using K-mean clustering analysis, we grouped DEGs into 7 clusters and gene names and genebank accession numbers between 2 and 6 were arranged. Additionally, the functional groups of human biomarker candidates were organized and compared between non-PD vs. PD and non-PD vs. Parkin. Finally, PD-related differentially regulated genes by oxidative stress were categorized among non-PD, PD and Parkin. Conclusions: This study showed that knowledge of selective gene expression profile derived from PD patients might potentially lead to better understanding of PD pathology and development of early diagnosis and effective therapy targeted their human biomarkers.
Pak, Jaewoo,Lee, Jung Hun,Park, Kwang Seung,Park, Moonhee,Kang, Lin-Woo,Lee, Sang Hee BioMed Central 2017 JOURNAL OF BIOMEDICAL SCIENCE -BASEL- Vol.24 No.1
<P>Autologous adipose stromal vascular fractions (SVFs) containing adipose tissue-derived stem cells (ASCs) are currently being used in clinical settings for various orthopedic applications for human patients. Due to its potential capability of regenerating cartilage, bone, and tendons, autologous adipose SVFs are being tried in treating patients with osteoarthritis (OA), chondromalacia, meniscus tear, osteonecrosis of the femoral head, and tendon injuries. Here, we have reviewed available human clinical studies with regard to patient applications of autologous adipose SVF containing ASCs, specifically assessing effectiveness and safety in the field of orthopedic disorders. All studies reviewed in this article presents potential benefits of autologous adipose SVF in various orthopedic applications without any serious side effects.</P>
Coculture Effects on the Osteogenic Differentiation of Human Mesenchymal Stromal Cells
Astghik Hayrapetyan,Soraya Surjandi,Evita EPJ Lemsom,Marleen MMW Wolters,John A Jansen,Jeroen JJP van den Beucken 한국조직공학과 재생의학회 2016 조직공학과 재생의학 Vol.13 No.6
Cell-based bone regeneration is generally pursued based on single cell type approaches, for which human adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used, owing to their easy accessibility and relatively large yield. In view of multiple cell types involved in physiological bone regeneration, this study aimed to evaluate the osteogenic differentiation of AT-MSCs upon co-culture with endothelial cells or macrophages in a direct or indirect in vitro co-culture set-up. Our hypotheses were that 1) endothelial cells and macrophages stimulate AT-MSCs proliferation and osteogenic differentiation and that 2) these two cell types will more profoundly affect osteogenic differentiation of AT-MSCs in a direct compared to an indirect co-culture set-up, because of the possibility for both cell-cell interactions and effects of secreted soluble factors in the former. Osteogenic differentiation of AT-MSCs was stimulated by endothelial cells, particularly in direct co-cultures. Although initial numbers of AT-MSCs in co-culture with endothelial cells were 50% compared to monoculture controls, equal levels of mineralization were achieved. Macrophages showed a variable effect on AT-MSCs behavior for indirect co-cultures and a negative effect on osteogenic differentiation of AT-MSCs in direct co-cultures, the latter likely due to species differences of the cell types used. The results of this study demonstrate potential for cell combination strategies in bone regenerative therapies.
Proangiogenic Hypoxia-Mimicking Agents Attenuate Osteogenic Potential of Adipose Stem/Stromal Cells
Abu-Shahba Ahmed G.,Gebraad Arjen,Kaur Sippy,Paananen Riku O.,Peltoniemi Hilkka,Seppänen-Kaijansinkko Riitta,Mannerström Bettina 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.4
BACKGROUND: Insufficient vascularization hampers bone tissue engineering strategies for reconstructing large bone defects. Delivery of prolyl-hydroxylase inhibitors (PHIs) is an interesting approach to upregulate vascular endothelial growth factor (VEGF) by mimicking hypoxic stabilization of hypoxia-inducible factor-1alpha (HIF-1α). This study assessed two PHIs: dimethyloxalylglycine (DMOG) and baicalein for their effects on human adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs). METHODS: Isolated AT-MSCs were characterized and treated with PHIs to assess the cellular proliferation response. Immunostaining and western-blots served to verify the HIF-1α stabilization response. The optimized concentrations for long-term treatment were tested for their effects on the cell cycle, apoptosis, cytokine secretion, and osteogenic differentiation of AT-MSCs. Gene expression levels were evaluated for alkaline phosphatase (ALPL), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor A (VEGFA), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). In addition, stemness-related genes Kruppel-like factor 4 (KLF4), Nanog homeobox (NANOG), and octamer-binding transcription factor 4 (OCT4) were assessed. RESULTS: PHIs stabilized HIF-1α in a dose-dependent manner and showed evident dose- and time dependent antiproliferative effects. With doses maintaining proliferation, DMOG and baicalein diminished the effect of osteogenic induction on the expression of RUNX2, ALPL, and COL1A1, and suppressed the formation of mineralized matrix. Suppressed osteogenic response of AT-MSCs was accompanied by an upregulation of stemness-related genes. CONCLUSION: PHIs significantly reduced the osteogenic differentiation of AT-MSCs and rather upregulated stemness-related genes. PHIs proangiogenic potential should be weighed against their longterm direct inhibitory effects on the osteogenic differentiation of AT-MSCs.