Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insight.
Systemically administered allogeneic mesenchymal stem cells do not aggravate the progression of precancerous lesions: a new biosafety insight.
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DOI：
10.1186/s13287-018-0878-1
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发表时间：
2018-05-11
影响因子：
7.5
通讯作者：
Conget P
中科院分区：
文献类型：
--
作者：
Bruna F;Plaza A;Arango M;Espinoza I;Conget P
间充质干细胞（MSC）是基质细胞的异质子集，目前已测试用于多种治疗目的。它们具有进入肿瘤、分泌营养/血管生成因子以及抑制免疫反应的潜力，这引发了有关其生物安全性的问题。我们的目的是评估全身施用同种异体间充质干细胞是否会改变癌前病变的自然进展，以及它们的推定效果是否取决于癌症分期和/或细胞剂量。通过在一个颊囊中局部施用 7,12-二甲基苯并[a]蒽，在叙利亚金仓鼠中诱发口腔鳞状细胞癌 (OSCC)。在增生、发育不良或乳头状瘤阶段，动物心内接受媒介物或0.7× 106、7× 106或21 × 106同种异体骨髓来源的MSC/kg。根据红斑和白斑的存在、炎症和血管化的程度以及肿瘤的外观、体积和分期来评估 OSCC 的进展。此外，还研究了供体细胞的归巢。癌前病变在2周内从增生进展为不典型增生，在3周内从不典型增生进展为乳头状瘤，在4周内从乳头状瘤进展为癌。在增生或发育不良阶段全身施用 MSC 不会改变该时间进程。当在乳头状瘤阶段施用间充质干细胞时，病变并未进展至癌症阶段。在增生阶段接受 0.7 × 106 或 7 × 106 MSCs/kg 的仓鼠中形成的肿瘤明显小于对照动物中发现的肿瘤（25 ± 4 或 23 ± 4 mm3 与 72 ± 19 mm3，p < 0.05）。当在乳头状瘤阶段施用 0.7 × 106、7 × 106 或 21 × 106 MSCs/kg 时，获得了类似的结果（44 ± 15、28 ± 7 或 28 ± 5 mm3 与 104 ± 26 mm3、 p < 0.05）。对于发育不良阶段，只有较低浓度的 MSC 达到统计学显着性（21±±9 mm3 与 94±±39 mm3，p<±0.05）。在增生阶段接受 21 × 106 MSCs/kg 的动物产生的肿瘤比接受载体的动物中发现的肿瘤更大（147± 47 mm3 与 72 ± 19 mm3，p< 0.05）。在癌前病变中很少发现供体细胞。全身施用同种异体间充质干细胞不会加剧癌前病变的进展。此外，它们还可以阻止癌症进展和肿瘤生长。本文的在线版本 (10.1186/s13287-018-0878-1) 包含补充材料，可供授权用户使用。
Mesenchymal stem cells (MSCs) are a heterogeneous subset of stromal cells currently tested for multiple therapeutic purposes. Their potential to home into tumors, to secrete trophic/vasculogenic factors, and to suppress immune response raises questions regarding their biosafety. Our aim was to evaluate whether systemically administered allogeneic MSCs modify the natural progression of precancerous lesions and whether their putative effect depends on cancer stage and/or cell dose. Oral squamous cell carcinoma (OSCC) was induced in Syrian golden hamsters by topical application of 7,12-dimethylbenz[a]anthracene in one buccal pouch. At hyperplasia, dysplasia, or papilloma stage, animals received intracardially the vehicle or 0.7 × 106, 7 × 106, or 21 × 106 allogeneic bone marrow-derived MSCs/kg. OSCC progression was assessed according to the presence of erythroplakia and leukoplakia, extent of inflammation and vascularization, and appearance, volume, and staging of tumors. Also, the homing of donor cells was studied. Precancerous lesions progressed from hyperplasia to dysplasia in 2 weeks, from dysplasia to papilloma in 3 weeks, and from papilloma to carcinoma in 4 weeks. This time course was unmodified by the systemic administration of MSCs at hyperplasia or dysplasia stages. When MSCs were administered at papilloma stage, lesions did not progress to carcinoma stage. Tumors developed in hamsters receiving 0.7 × 106 or 7 × 106 MSCs/kg at hyperplasia stage were significantly smaller than those found in control animals (25 ± 4 or 23 ± 4 mm3 versus 72 ± 19 mm3, p < 0.05). Similar results were obtained when 0.7 × 106, 7 × 106, or 21 × 106 MSCs/kg were administered at papilloma stage (44 ± 15, 28 ± 7, or 28 ± 5 mm3 versus 104 ± 26 mm3, p < 0.05). For dysplasia stage, only the lower concentration of MSCs reached statistical significance (21 ± 9 mm3 versus 94 ± 39 mm3, p < 0.05). Animals receiving 21 × 106 MSCs/kg at hyperplasia stage developed tumors larger than those found in animals that received the vehicle (147 ± 47 mm3 versus 72 ± 19 mm3, p < 0.05). Donor cells were rarely found in precancerous lesions. Systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth. The online version of this article (10.1186/s13287-018-0878-1) contains supplementary material, which is available to authorized users.
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影响因子：
7.5
作者：
Morando S;Vigo T;Esposito M;Casazza S;Novi G;Principato MC;Furlan R;Uccelli A
通讯作者：
Uccelli A
影响因子：
2.9
作者：
SCHWARTZ, J;SHKLAR, G;TRICKLER, D
通讯作者：
TRICKLER, D
DOI：
10.1001/jama.2012.25321
发表时间：
2012-12-12
期刊：
JAMA
影响因子：
--
作者：
Hare JM;Fishman JE;Gerstenblith G;DiFede Velazquez DL;Zambrano JP;Suncion VY;Tracy M;Ghersin E;Johnston PV;Brinker JA;Breton E;Davis-Sproul J;Schulman IH;Byrnes J;Mendizabal AM;Lowery MH;Rouy D;Altman P;Wong Po Foo C;Ruiz P;Amador A;Da Silva J;McNiece IK;Heldman AW;George R;Lardo A
通讯作者：
Lardo A
影响因子：
4.6
作者：
Hamamoto, Hirotsugu;Gorman, Joseph H., III;Ryan, Liam P.;Hinmon, Robin;Martens, Timothy P.;Schuster, Michael D.;Plappert, Theodore;Kiupel, Matti;John-Sutton, Martin G. St.;Itescu, Silviu;Gorman, Robert C.
通讯作者：
Gorman, Robert C.
影响因子：
5.2
作者：
Klopp, Ann H.;Gupta, Anshul;Spaeth, Erika;Andreeff, Michael;Marini, Frank, III
通讯作者：
Marini, Frank, III