Identification of Prognostic Biomarkers of Adipose-Derived Stem Cells Treatment in Non-healing Vascular Leg Ulcers

医学 金标准(测试) 伤口愈合 川地34 干细胞 脂肪组织 CD146号 内科学 外科 病理 遗传学 生物
作者
Maria Grazia Sibilla,I Zollino,Diana Campioni,Mirko Tessari,Anna Maria Malagoni,Paolo Zamboni
出处
期刊:European Journal of Vascular and Endovascular Surgery [Elsevier BV]
卷期号:58 (6): e407-e408
标识
DOI:10.1016/j.ejvs.2019.06.1049
摘要

Introduction - Autologous adipose tissue-derived stem cells (ASCs) has shown great potential in wound healing for patients not responder to gold standard tratment1-2. However, with easier isolation and better availability ASCs have sparked great clinical and research interest 3. The aim of our study is to identify biomarkers predictive of successful cell treatment in non healing vascular leg ulcers (VLU) using a reproducible technical approach verified in parallel with a deep lab cell characterization. Methods - From an initial cohort of 38 patients, 16 patients affected by non healing VLUs were randomized respectively to gold standard treatment (control arm,5 men 3 women) and to gold standard treatment plus ASCs (experimental arm, 5 men 3 women) sampling according to Coleman's technique4. The sample was centrifuged at 1300 r / min for 3 minutes and injected with an 18 G needle into the edges and into the bed of ulcer. A sample of lipoaspirate was sent simultaneously to the laboratory where it was appropriately treated for FVS extraction5. The cells are incubated with different monoclonal antibodies in order to quantify and characterize the different stem cells present (CD45-CD34 +, CD34 + CD146 +/- etc.). The next step involved the evaluation of cellular clonogenicity to estimate in vitro the number of aggregated fibroblasts (Unit Forming Colonies, CFU-F). The different immunophenotypical and functional characteristic of the harvested ASCs were correlated with clinical outcomes respectively: healing time, pain measured by NRS scale, Margolix index (MI)6, complete healing. Results - No major adverse events were recorded. The healing process was significantly faster by applying ASCs, 17.5± 7.0 weeks vs 24.5 ± 4.9 weeks recorded in the control arm (p<0.036). NRS dropped after the first week to 2.7 ± 2.0 in the experimental arm vs 6.6 ± 3.0, in the controls (p < 0.01). The MI was not significantly different between arms. Very interestingly we found a strong reverse correlation between the % of CD34+/CD45- cells respectively with the healing time (r= -0.894, p<0.041) and NRS (r=-0.934, p<0.020). Moreover, the in vitro expanded non hematopoietic progenitor (expressed as a N° of CFU-F) present an inverted correlation with the healing time (r=-0.868, p<0.057) while a significant correlation with NRS (r=-0.883, p<0.047) (Fig.1). There was also a positive correlation between the MI and the % of the CD34+ cells (r = 0.94 p < 0.005). The relationship between the MI and % of CFU-F is significantly associated (r=0.97 p < 0.002), as is also the correlation between MI with the total number of calculated CFU-F reinfused (r=0.98 p < 0.002). Finally, the number of pericytes described as the % of CD146+/CD271-CD45 low cells correlate significantly with the MI (r = 0.98 p < 0.002). Conclusion - The percentage % of CD34+/CD45- cells seems a predictive biomarker of successful ASCs treatment in these patients. References1.Galipeau J, Krampera M, Barrett J, Dazzi F, Deans RJ, Debruijn J, et al. International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials. Cytotherapy 2016;18(2):151-9.2.Sousa BR, Parreira RC, Fonseca EA, Amaya MJ, Tonelli FMP, Lacerda SMSN, et al. Human adult stem cells from diverse origins: an overview from multiparametric immunophenotyping to clinical application. Cytometry Part A 2014;85(1):43-77.3.Gimble JM, Bunnell BA, Guilak F. Hum an adipose-derived cells: an update on the transition to clinical translation. Regen Med 2012;7(2):225-35.4.Zollino I, Zuolo M, Gianesini S, Pedriali M, Sibilla MG, Tessari M, et al. Autologous adipose-derived stem cells: basic science, technique, and rationale for application in ulcer and wound healing. Phlebology 2017;32(3):160-71.5.Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 2001;7(2):211-28.6.Kantor J, Margolis DJ. A multicentre study of percentage change in venous leg ulcer area as a prognostic index of healing at 24 weeks. Br J Dermatol 2000;142(5):960-4.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
bkagyin应助科研通管家采纳,获得10
1秒前
隐形曼青应助科研通管家采纳,获得10
1秒前
彭于晏应助科研通管家采纳,获得10
1秒前
FashionBoy应助科研通管家采纳,获得10
1秒前
1秒前
科研通AI5应助科研通管家采纳,获得10
1秒前
汉堡包应助科研通管家采纳,获得10
1秒前
1秒前
1秒前
hnu301完成签到,获得积分10
2秒前
英姑应助冷酷鱼采纳,获得10
3秒前
3秒前
屿落完成签到,获得积分10
3秒前
昏睡的蟠桃应助zzz采纳,获得100
3秒前
量子星尘发布了新的文献求助10
5秒前
恋雅颖月应助幸福大白采纳,获得10
5秒前
wh完成签到,获得积分10
5秒前
余淮完成签到,获得积分10
6秒前
平淡的初翠完成签到,获得积分10
6秒前
快乐一江发布了新的文献求助10
7秒前
邱型程应助屿落采纳,获得20
8秒前
鹤鸣完成签到,获得积分10
11秒前
11秒前
11秒前
13秒前
天真的高山完成签到,获得积分10
14秒前
善良海云完成签到,获得积分10
16秒前
ANG发布了新的文献求助10
16秒前
从容梦旋完成签到,获得积分10
18秒前
19秒前
酷波er应助liuyunhao7207采纳,获得10
19秒前
人生如梦应助健忘跳跳糖采纳,获得10
20秒前
20秒前
sihanzhiyu发布了新的文献求助10
20秒前
汉堡包应助dpp采纳,获得10
20秒前
在水一方应助hnu301采纳,获得10
20秒前
jbhb完成签到,获得积分20
21秒前
Colossus完成签到,获得积分10
21秒前
21秒前
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989406
求助须知:如何正确求助?哪些是违规求助? 3531522
关于积分的说明 11254187
捐赠科研通 3270174
什么是DOI,文献DOI怎么找? 1804901
邀请新用户注册赠送积分活动 882105
科研通“疑难数据库(出版商)”最低求助积分说明 809174