scholarly journals Infrapatellar fat pad-derived mesenchymal stromal cells from osteoarthritis patients: In vitro genetic stability and replicative senescence

2016 ◽  
Vol 35 (5) ◽  
pp. 1029-1037 ◽  
Author(s):  
Simona Neri ◽  
Serena Guidotti ◽  
Nicoletta Libera Lilli ◽  
Luca Cattini ◽  
Erminia Mariani
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Genetic Stability ◽  
Replicative Senescence ◽  
Infrapatellar Fat Pad ◽  
Fat Pad

scholarly journals The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Knee Arthroscopy ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Knee Cartilage ◽  
Fat Pad ◽  
Group 12 ◽  
Significant Difference

Abstract Introduction To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method. Methods Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6 weeks, 12 weeks, 6 months, and 12 months after intervention. MORCART scores were assessed at pre-operation and 12 months after intervention. Results Twenty-nine cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P > 0.05). The WOMAC total and WOMAC function scores of the experiment group were significantly lower than those of the control group 6 months and 12 months after surgery (P < 0.05). The VAS rest and VAS motion scores of the experiment group were found significantly lower than those of the control group 12 months after surgery (P < 0.05). The MOCART scores of the experiment group were found significantly higher compared with the control group 12 months after surgery (P < 0.05). No significant difference in WOMAC stiffness scores were found between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe and provides assistance in reducing pain and improving function in patients with knee cartilage lesions. Trial registration ChiCTR1800015379. Registered on 27 March 2018, http://www.chictr.org.cn/showproj.aspx?proj=25901.

scholarly journals CD146+CD107a+ Mesenchymal Stem/Stromal Cells with Signature Attributes Correlate to Therapeutic Potency as “First Responders” to Injury and Inflammation

2019 ◽  
Author(s):  
Annie C. Bowles ◽  
Dimitrios Kouroupis ◽  
Melissa A. Willman ◽  
Carlotta Perucca Orfei ◽  
Ashutosh Agarwal ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Immune Cell ◽  
First Responders ◽  
Infrapatellar Fat Pad ◽  
M2 Macrophage ◽  
List Type ◽  
Fat Pad ◽  
Secretory Capacity

ABSTRACTCD146+ bone marrow–derived Mesenchymal Stem/Stromal Cells (BM-MSC) play key roles in the perivascular niche, skeletogenesis and hematopoietic support, however elucidation of therapeutic potency has yet to be determined. Here, inflammatory challenge to crude BM-MSC captured a baseline of signatures including enriched expression of CD146+ with CD107a+, CXCR4+, and LepR+, transcriptional profile, enhanced secretory capacity, robust secretome and immunomodulatory function with stimulated target immune cells. These responses were significantly more pronounced in CD146+ (POS)-selected subpopulation than in the CD146- (NEG). Mechanistically, POS uniquely mediated robust immunosuppression while inducing significant frequencies of Naïve and Regulatory T cells in vitro. Moreover, POS promoted a pivotal M1-to-M2 macrophage shift in vivo, ameliorating inflammation/fibrosis of joint synovium and fat pad of the knee, failed by NEG. This study provides high-content evidence of CD146+CD107a+ BM-MSC, herein deemed ‘first responders’ to inflammation, as the underrepresented subpopulation within crude BM-MSC with innately higher secretory capacity and therapeutic potency.HIGHLIGHTSSignature phenotypic, transcriptional, and secretome profiles were identified and enriched in human CD146+ (POS)-selected subpopulation in response to inflammationInflammatory challenge consistently altered stemness (LIF) and differentiation master regulators (SOX9, RUNX2, PPARγ) in crude, POS, and NEG BM-MSC, and deduced unique expressions in POS compared to NEGPOS BM-MSC mediated the strongest immunomodulation, e.g. target immune cell suppression, Treg induction, diminished T cell differentiationPOS BM-MSC promoted the largest M1-to-M2 shift in vivo alleviating induced synovitis and infrapatellar fat pad fibrosis of the knee

Regulatory-compliant conditions during cell product manufacturing enhance in vitro immunomodulatory properties of infrapatellar fat pad-derived mesenchymal stem/stromal cells

Cytotherapy ◽  
2020 ◽  
Vol 22 (11) ◽  
pp. 677-689
Author(s):  
Dimitrios Kouroupis ◽  
Annie C. Bowles ◽  
Dylan N. Greif ◽  
Clarissa Leñero ◽  
Thomas M. Best ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Cell Product ◽  
Product Manufacturing ◽  
Immunomodulatory Properties

scholarly journals The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: A Prospective, Randomized and Controlled Study

2021 ◽  
Author(s):  
Yiqin Zhou ◽  
Haobo Li ◽  
Dong Xiang ◽  
Jiahua Shao ◽  
Qiwei Fu ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Knee Arthroscopy ◽  
Infrapatellar Fat Pad ◽  
Control Group ◽  
Knee Cartilage ◽  
Fat Pad ◽  
Group 12 ◽  
Significant Difference

Abstract Background: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method.Methods: 60 cases from Shanghai Changzheng Hospital during April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy. VAS and WOMAC scores were assessed at pre-operation, and 6-weeks, 12-weeks, 6-months, and 12-months after intervention. MORCART scores were assessed at pre-operation and 12-months after intervention.Results: 29 cases in the experiment group and 28 cases in the control group were followed up. No significant difference in VAS, WOMAC, and MOCART scores were found between the two groups before surgery (P>0.05). The WOMAC-Total and WOMAC-Function scores of experiment group were significantly lower than those of control group 6 months, 12 months after surgery (P<0.05). The VAS-Rest and VAS-Motion scores of experiment group were found significantly lower than those of control group 12 months after surgery (P<0.05). The MOCART scores of experiment group were found significant higher compared with control group 12 months after surgery (P<0.05). No significant difference in WOMAC-Stiffness scores were found between the two groups. Conclusions: The short-term results of our study are encouraging and demonstrate that knee arthroscopy with infrapatellar fat pad cell concentrates containing mesenchymal stromal cells is safe, and provides assistance in reducing pain and improving function in patients with knee cartilage lesions.

scholarly journals Hybrid complexes of high and low molecular weight hyaluronan delay in vitro replicative senescence of mesenchymal stromal cells: a pilot study for future therapeutic application

Aging ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 1575-1585 ◽  
Author(s):  
Nicola Alessio ◽  
Antonietta Stellavato ◽  
Tiziana Squillaro ◽  
Stefania Del Gaudio ◽  
Giovanni Di Bernardo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Pilot Study ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Low Molecular Weight ◽  
Therapeutic Application ◽  
Hybrid Complexes

scholarly journals Human adipose-derived mesenchymal stromal cells from face and abdomen undergo replicative senescence and loss of genetic integrity after long-term culture

2021 ◽  
Author(s):  
Priscilla B Delben ◽  
Helena D Zomer ◽  
Camila A Silva ◽  
Rogerio S Gomes ◽  
Fernanda R Melo ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Replicative Senescence ◽  
Genetic Integrity ◽  
Cell Therapies ◽  
Long Term Culture ◽  
Morphological Alterations ◽  
Fat Depots

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization, but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-β-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γH2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.

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