Freeze-dried and GMP-compliant pharmaceuticals containing exosomes for acellular mesenchymal stromal cell immunomodulant therapy

被引：109

作者：

Bari, Elia ^{[1
]}

Perteghella, Sara ^{[1
,2
]}

Catenacci, Laura ^{[1
]}

Sorlini, Marzio ^{[2
,3
]}

Croce, Stefania ^{[4
]}

Mantelli, Melissa ^{[5
]}

Avanzini, Maria A. ^{[5
]}

Sorrenti, Milena ^{[1
]}

Torre, Maria L. ^{[1
,2
]}

机构：

[1] Univ Pavia, Dept Drug Sci, Viale Taramelli 12, I-27100 Pavia, Italy

[2] PharmaExceed Srl, I-27100 Pavia, Italy

[3] Univ Appl Sci & Arts Southern Switzerland, Dept Innovat Technol, SUPSI, Via Pobiette 11, CH-6928 Manno, Switzerland

[4] Univ Pavia, Dept Clin Surg Diagnost & Pediat Sci, I-27100 Pavia, Italy

[5] Fdn IRCCS Policlin S Matteo, Immunol & Transplantat Lab, Pediat Surg Cell Factory & Regenerat Med Res Ctr, I-27100 Pavia, Italy

来源：

NANOMEDICINE | 2019年 / 14卷 / 06期

关键词：

adipose tissue; bone marrow; exosome; extracellular vesicles; freeze-drying; immunomodulation; mesenchymal stromal cells; secretome; ultracentrifugation; ultrafiltration; EXTRACELLULAR VESICLES; STEM-CELLS; ULTRAFILTRATION; TISSUE; YIELD;

D O I：

10.2217/nnm-2018-0240

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 [微生物学]; 090105 [作物生产系统与生态工程];

摘要：

Aim: To validate the use of ultrafiltration (UF) as an alternative applicable industrial method to replace ultracentrifugation (UC) in the purification of mesenchymal stromal cell (MSC)-secretome. Materials & methods: Pharmaceutical formulations containing secretome and/or extracellular vesicles were extracted from adipose-MSCs and bone marrow-MSCs by combining UF or UC with lyophilization. Results & conclusion: UF led to higher protein, lipid, cytokine and exosomes yields compared with UC. The isolation procedure and cell source influenced immunomodulatory activity, which was in vitro evaluated by inhibition of phytohemagglutinin-activated peripheral blood mononuclear cell proliferation, and by modulation of IL-10, IFN-gamma and IL-6. A secretome dosage was identified to obtain the same immunomodulatory activity of MSCs, paving the way for cell-free therapy.

引用

页码：753 / 765

页数：13

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