Background: Recently, cell-based therapeutic lymphangiogenesis has emerged and provided hope for lymphatic regeneration. Previous studies have demonstrated that secretomes of mesenchymal stem cells (MSCs) facilitate the regeneration of various damaged tissues. This study was conducted to evaluate the lymphangiogenic potential of hypoxic conditioned media (HCM) from MSCs. Methods: To investigate the effects of MSC-secreted factors in starved human lymphatic endothelial cells (hLEC), hLECs were treated with endothelial basal medium (EBM)-2 (control), normoxic conditioned media (NCM), or HCM in vitro and in vivo. Results: MSCs expressed lymphangiogenic factors including EGF, FGF2, HGF, IGF-1, and VEGF-A and -C. hLECs were treated with each medium. hLEC proliferation, migration, and tube formation were improved under HCM compared with NCM. Moreover, expression of mitochondrial-related factors, MFN1and 2, were improved in HCM-treated hLECs. Lymphedema mice injected with HCM showed markedly decreased lymphedema via increased lymphatic vessel formation when compared with EBM-2- or NCM-treated mice. Conclusions: This study suggested that HCM from MSCs contain high levels of secreted lymphangiogenic factors and promote lymphangiogenesis by regulating mitochondrial-related factors. Thus, treatment with HCM may be a therapeutic strategy for lymphedema.

Kim K, et al. Ann Rehabil Med. 2017 Apr;41(2):266-272. https://doi.org/10.5535/arm.2017.41.2.266

You Gyoung Yi, Hyung-Ik Shin, and Dae-Hyun Jang. J Genet Med 2020;17:55-61. https://doi.org/10.5734/JGM.2020.17.2.55

Hae-Yeon Park, M.D., Myungshin Kim, M.D., Woori Jang, M.D., and Dae-Hyun Jang, M.D.. Ann Lab Med 2017;37:563-5. https://doi.org/10.3343/alm.2017.37.6.563

Despite the current widespread use of chromosomal microarray analysis (CMA) and exome/genome sequencing for the genetic diagnosis of unexplained intellectual disability (ID) in children, gaining improved diagnostic yields and defined guidelines remains a significant challenge. This is a cohort study of children with unexplained ID. We analyzed the diagnostic yield and its correlation to clinical phenotypes in children with ID who underwent concurrent CMA and clinical exome sequencing (CES). A total of 154 children were included (110 [71.4%] male; mean [SD] age, 51.9 [23.1] months). The overall diagnosis yield was 26.0–33.8%, with CMA contributing 12.3–14.3% and CES contributing 13.6–19.4%, showing no significant difference. The diagnostic rate was significantly higher when gross motor delay (odds ratio, 6.69; 95% CI, 3.20–14.00; P < 0.001), facial dysmorphism (odds ratio, 9.34; 95% CI 4.29–20.30; P < 0.001), congenital structural anomaly (odds ratio 3.62; 95% CI 1.63–8.04; P = 0.001), and microcephaly or macrocephaly (odds ratio 4.87; 95% CI 2.05–11.60; P < 0.001) were presented. Patients with only ID without any other concomitant phenotype (63/154, 40.9%) exhibited a 6.3–11.1% diagnostic rate.