低温保存脂肪来源的间充质基质细胞作为细胞治疗产品储存和分发的可行解决方案。

Hypothermic Preservation of Adipose-Derived Mesenchymal Stromal Cells as a Viable Solution for the Storage and Distribution of Cell Therapy Products.

作者信息

Branco André, Tiago Ana L, Laranjeira Paula, Carreira Maria C, Milhano João C, Dos Santos Francisco, Cabral Joaquim M S, Paiva Artur, da Silva Cláudia L, Fernandes-Platzgummer Ana

机构信息

Department of Bioengineering and Institute for Bioengineering and Biosciences (iBB), Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal.

Associate Laboratory i4HB-Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisbon, Portugal.

出版信息

Bioengineering (Basel). 2022 Dec 14;9(12):805. doi: 10.3390/bioengineering9120805.

Abstract

Cell and gene therapies (CGT) have reached new therapeutic targets but have noticeably high prices. Solutions to reduce production costs might be found in CGT storage and transportation since they typically involve cryopreservation, which is a heavily burdened process. Encapsulation at hypothermic temperatures (e.g., 2-8 °C) could be a feasible alternative. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)) expanded using fetal bovine serum (FBS)- (MSC-FBS) or human platelet lysate (HPL)-supplemented mediums (MSC-HPL) were encapsulated in alginate beads for 30 min, 5 days, and 12 days. After bead release, cell recovery and viability were determined to assess encapsulation performance. MSC identity was verified by flow cytometry, and a set of assays was performed to evaluate functionality. MSC(AT) were able to survive encapsulated for a standard transportation period of 5 days, with recovery values of 56 ± 5% for MSC-FBS and 77 ± 6% for MSC-HPL (which is a negligible drop compared to earlier timepoints). Importantly, MSC function did not suffer from encapsulation, with recovered cells showing robust differentiation potential, expression of immunomodulatory molecules, and hematopoietic support capacity. MSC(AT) encapsulation was proven possible for a remarkable 12 day period. There is currently no solution to completely replace cryopreservation in CGT logistics and supply chain, although encapsulation has shown potential to act as a serious competitor.

摘要

细胞和基因疗法(CGT)已实现新的治疗靶点,但价格显著高昂。由于CGT通常涉及冷冻保存,这是一个负担沉重的过程,因此在CGT储存和运输中可能会找到降低生产成本的解决方案。低温(例如2-8°C)封装可能是一种可行的替代方案。将使用胎牛血清(FBS)(MSC-FBS)或添加人血小板裂解物(HPL)的培养基(MSC-HPL)扩增的脂肪组织来源的间充质基质细胞(MSC(AT))封装在藻酸盐珠中30分钟、5天和12天。珠子释放后,测定细胞回收率和活力以评估封装性能。通过流式细胞术验证MSC身份,并进行一组测定以评估功能。MSC(AT)能够在封装状态下存活5天的标准运输期,MSC-FBS的回收率为56±5%,MSC-HPL的回收率为77±6%(与早期时间点相比,下降可忽略不计)。重要的是,MSC功能不受封装影响,回收的细胞显示出强大的分化潜力、免疫调节分子表达和造血支持能力。已证明MSC(AT)可以封装长达12天。尽管封装已显示出成为有力竞争对手的潜力,但目前在CGT物流和供应链中尚无完全替代冷冻保存的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e4b/9774331/4ae59cddd34f/bioengineering-09-00805-g001.jpg

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