Labrador Velandia Sonia, Di Lauro Salvatore, Alonso-Alonso Maria Luz, Tabera Bartolomé Soraya, Srivastava Girish Kumar, Pastor José Carlos, Fernandez-Bueno Ivan
Instituto Universitario de Oftalmobiología Aplicada (IOBA), Retina Group, University of Valladolid, Campus Miguel Delibes, Paseo de Belén 17, 47011, Valladolid, Spain.
Department of Ophthalmology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
Graefes Arch Clin Exp Ophthalmol. 2018 Jan;256(1):125-134. doi: 10.1007/s00417-017-3842-3. Epub 2017 Nov 22.
To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits.
Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 10 cells/ml. Groups 3 and 6 received a high dose of 30 × 10 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs.
There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected.
MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 10 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.
评估在具有免疫活性的有色兔眼玻璃体内注射人骨髓间充质干细胞（MSCs）的可行性、安全性和生物相容性。
32只有色兔（24只雌性，8只雄性；青紫蓝兔-新西兰白兔）分为8组，每组4只动物。将商业制备的人骨髓间充质干细胞（0.05 ml）注射到右眼晶状体后的玻璃体中。第1组和第4组接受等渗介质（基于乳酸林格液），第2组、第5组、第7组和第8组接受低剂量15×10⁶细胞/ml。第3组和第6组接受高剂量30×10⁶细胞/ml。在注射骨髓间充质干细胞前及之后每周进行2周或6周评估并记录临床体征。注射后2周或6周处死动物。通过组织学和荧光原位杂交评估眼睛、肝脏、脾脏和性腺，以评估骨髓间充质干细胞的存活和眼外迁移情况。
在任何时间点，对照兔眼和注射骨髓间充质干细胞的兔眼之间均未发现相关临床结果。在对照兔和注射骨髓间充质干细胞的兔之间，也未发现与眼、肝、脾或性腺组织改变相关的组织学结果。注射后骨髓间充质干细胞在玻璃体内至少存活2周。未检测到骨髓间充质干细胞的眼外迁移。
在有色兔眼中以15×10⁶细胞/ml的剂量玻璃体内注射骨髓间充质干细胞是安全且耐受性良好的。这些发现为未来在视网膜疾病临床试验中探索商业制备的同种异体人骨髓间充质干细胞的玻璃体内应用研究提供了可能。
