Review
Pharmacology & Pharmacy
Takeo Mukai, Kenshi Sei, Tokiko Nagamura-Inoue
Summary: Studies show that MSCs exert neuroprotective and neurorestorative effects by secreting neurotrophic factors, and clinical trials have confirmed their efficacy in treating neurological disorders, highlighting the promising progress in this field.
Article
Biochemistry & Molecular Biology
Yeping Yu, Qiqi Zhang, Ning Wu, Lei Xia, Jie Cao, Qiang Xia, Jie Zhao, Jianjun Zhang, Hualian Hang
Summary: Human umbilical cord mesenchymal stem/stromal cells (hUMSCs) overexpressing hepatocyte nuclear factor 4 alpha (HNF4 alpha) showed better therapeutic effects on acute liver failure (ALF) compared to hUMSCs without HNF4 alpha overexpression. The overexpression of HNF4 alpha enhanced IL-10 transcription and promoted M2 macrophage polarization through the IL-10/STAT3 pathway. This study suggests that HNF4 alpha-hUMSCs could serve as a novel therapy for ALF.
Article
Pharmacology & Pharmacy
Huanjie Chen, Yulong Luo, Yiping Zhu, Yongshun Ye, Difei Chen, Xinyu Song, Zhulin Xiao, Ming Liu, Shiyue Li
Summary: In this study, UCMSCs overexpressing hepatocyte growth factor (HGF) were used to treat pulmonary fibrosis. The results showed that HGF-UCMSCs significantly reduced fibrosis and improved lung function. The overexpression of HGF may enhance the anti-fibrotic effect of UCMSCs by interacting with interleukin-17-producing cells in fibrotic lungs.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Shashank Chetty, Reza Yarani, Ganesh Swaminathan, Rosita Primavera, Shobha Regmi, Sravanthi Rai, Jim Zhong, Abantika Ganguly, Avnesh S. Thakor
Summary: This review provides an overview of the sources, regenerative and immunomodulatory properties, clinical applications, therapeutic potential, biodistribution, and obstacles to translation of umbilical cord-mesenchymal stromal cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell & Tissue Engineering
Xiaoyun Wu, Zhijie Ma, Yuxiao Yang, Yongxu Mu, Daocheng Wu
Summary: In this study, the safety and biodistribution of intraperitoneally transplanted umbilical cord-derived MSCs (UCMSCs) were investigated. It was found that UCMSCs cultured in a serum-free, xeno-free, and chemically defined media (UCMSCs&SXFM-CD) exhibited improved safety profiles compared to UCMSCs cultured in serum-containing media (UCMSCsSCM), with no significant toxicity or tumorigenicity observed.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Cell & Tissue Engineering
Liyan Shi, Jing Ren, Jiping Li, Dongxu Wang, Yusu Wang, Tao Qin, Xiuying Li, Guokun Zhang, Chunyi Li, Yimin Wang
Summary: In this study, the therapeutic effects of umbilical cord-derived mesenchymal stromal cells (uMSCs) on pulmonary fibrosis (PF) were investigated, with a focus on their extracellular vesicles (uMSC-EVs) and specific miRNAs. The results suggest that uMSC-EVs alleviate PF by inhibiting the TGF-beta signaling pathway, with miR-21 and miR-23 playing critical roles in this process. This reveals a new potential strategy for PF treatment in clinical settings.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Oncology
Lucas Eduardo Botelho de Souza, Fernanda Ursoli Ferreira, Carolina Hassibe Thome, Heloisa Brand, Maristela Delgado Orellana, Vitor Marcel Faca, Aparecida Maria Fontes, Dimas Tadeu Covas
Summary: Melanoma cells have the capability to activate an EMT-like program and acquire metastatic traits through distinct pathways induced by MSCs' secretome, both in mouse and human cells.
Article
Neurosciences
Hao Lyu, Dong Ming Sun, Chi Ping Ng, Wendy S. Cheng, Jun Fan Chen, Yu Zhong He, Sin Yu Lam, Zhi Yuan Zheng, Guo Dong Huang, Chi Chiu Wang, Wise Young, Wai Sang Poon
Summary: This study investigated the effects of human umbilical cord blood (HUCB) mononuclear cell (MNC) therapy in a modified HIE rat model, demonstrating short and long term behavioral and histological improvements.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Adrienne Wright, Orman (Larry) Snyder, Hong He, Lane K. Christenson, Sherry Fleming, Mark L. Weiss
Summary: Many cell types, including cancer cells, release extracellular vesicles (EVs) that expose tissue factor (TF). It is unclear whether MSC-EVs have a risk of thromboembolism due to TF expression. In this study, the researchers investigated the expression of TF and the procoagulant activity of MSC-EVs. They also examined the impact of different EV isolation methods and cell culture expansion on EV yield, characterization, and potential risk. The results showed that MSC-EVs express TF and have procoagulant activity. Therefore, when using MSC-derived EVs as a therapeutic agent, considerations should be given to TF expression, procoagulant activity, and thromboembolism risk.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Cheng Ma, Xin Qi, Yi-Fan Wei, Zhi Li, He-Long Zhang, He Li, Feng-Lei Yu, Ya-Nan Pu, Yong-Can Huang, Yong-Xin Ren
Summary: This study introduced human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hUCMSC-EVs) as promising vehicles for the treatment of ligamentum flavum hypertrophy (LFH). By delivering miR-146a-5p and miR-221-3p, the hUCMSC-EVs significantly suppressed LFH and inhibited the activity of the TGF-beta/SMAD4 signaling pathway.
BIOACTIVE MATERIALS
(2023)
Article
Cell & Tissue Engineering
Hsiu-Chu Chou, Chien-Hsiang Chang, Chien-Han Chen, Willie Lin, Chung-Ming Chen
Summary: The consecutive intratracheal administration of surfactant and hUC-MSCs for two days effectively attenuated hyperoxia-induced lung injury in neonatal rats, demonstrating a potential therapeutic regimen for this condition.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Cell & Tissue Engineering
Charles Michael Cotten, Kimberley Fisher, William Malcolm, Kathryn E. Gustafson, Lynn Cheatham, Amanda Marion, Rachel Greenberg, Joanne Kurtzberg
Summary: Hypoxic ischemic encephalopathy (HIE) in neonates causes high mortality and long-term morbidity. Previous use of autologous cord blood for brain damage had limitations, while allogeneic cord tissue mesenchymal stromal cells (hCT-MSC) have shown promise. A phase I clinical trial was conducted to test the safety and efficacy of hCT-MSC in neonates with HIE, with positive results.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Cell & Tissue Engineering
Zan Tang, Junxiao Gao, Jie Wu, Guifang Zeng, Yan Liao, Zhenkun Song, Xiao Liang, Junyuan Hu, Yong Hu, Muyun Liu, Nan Li
Summary: HucMSC transplantation alleviates lung collagen accumulation and mortality in bleomycin-induced PF mice, promotes AT2 cell proliferation, inhibits lung fibroblast proliferation, and induces interferon-sensitive macrophages (IFNSMs) to secrete CXCL9 and CXCL10, recruiting more Treg cells to the injured lung.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Santina Acuto, Melania Lo Iacono, Elena Baiamonte, Rosa Lo Re, Aurelio Maggio, Vincenzo Cavalieri
Summary: This study optimized a method for isolating, propagating, and characterizing MSCs from human umbilical cords, resulting in the production of conditioned media with predictable composition and biological effects. This method has the potential for large-scale production of toxic-free conditioned media.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Obstetrics & Gynecology
Yoann Athiel, Jean-Marie Jouannic, Vincent Mauffre, Coralie Dehan, Clovis Adam, Stephane Blot, Pauline Lallemant, Timothe De Saint Denis, Jerome Larghero, Justine Nasone, Lucie Guilbaud
Summary: This study examines the effects of using an adjuvant allogenic umbilical cord mesenchymal stromal cell (UC-MSC) patch on motor and sphincter function in fetal surgery for myelomeningocele (MMC). The results show that the UC-MSC group had higher motor scores and a lower incidence of amyotrophy and incontinence compared to the control group. In addition, the UC-MSC group had less fibrosis and a higher density of large neurons in the spinal cord.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2023)
Review
Obstetrics & Gynecology
Makoto Nabetani, Takeo Mukai, Haruo Shintaku
Summary: The review discusses the brain damage process caused by neonatal HIE, introduces the roles of TH and cell therapies in protecting the newborn brain, and recent progress in using UC-MSCs for treating neurological disorders.
AMERICAN JOURNAL OF PERINATOLOGY
(2022)
Article
Pediatrics
Kennosuke Tsuda, Jun Shibasaki, Tetsuya Isayama, Akihito Takeuchi, Takeo Mukai, Tomoaki Ioroi, Akihito Takahashi, Hiroyuki Sano, Nanae Yutaka, Sachiko Iwata, Makoto Nabetani, Hisanori Sobajima, Shigeharu Hosono, Masanori Tamura, Osuke Iwata
Summary: This study found that body temperature plays a dual role in the outcome of newborn infants with encephalopathy, where low body temperature at admission and high body temperature during cooling are associated with adverse outcomes. Additionally, higher heart rates before and during cooling are also related to adverse outcomes. Further studies are needed to clarify the exact mechanism underlying the relationship between slightly higher body temperature during cooling and adverse outcomes.
PEDIATRIC RESEARCH
(2022)
Review
Neurosciences
Takeo Mukai, Kenshi Sei, Tokiko Nagamura-Inoue
Summary: MSCs have shown promising potential as a cell therapy for traumatic CNS injury, demonstrating feasibility and efficacy in clinical trials.
JOURNAL OF INTEGRATIVE NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Kennosuke Tsuda, Jun Shibasaki, Tetsuya Isayama, Akihito Takeuchi, Takeo Mukai, Yuichiro Sugiyama, Tomoaki Ioroi, Akihito Takahashi, Nanae Yutaka, Sachiko Iwata, Makoto Nabetani, Osuke Iwata
Summary: This study investigated the relationship between the severity of encephalopathy and 3-year clinical outcomes in high-survival infants who underwent therapeutic hypothermia. The results showed that while mortality rates were relatively low, the incidence of major disabilities was relatively high, possibly due to Japanese social and ethical norms.
SCIENTIFIC REPORTS
(2022)
Article
Pediatrics
Hirosato Aoki, Jun Shibasaki, Kennosuke Tsuda, Kouji Yamamoto, Akihito Takeuchi, Yuichiro Sugiyama, Tetsuya Isayama, Takeo Mukai, Tomoaki Ioroi, Nanae Yutaka, Akihito Takahashi, Takuya Tokuhisa, Makoto Nabetani, Osuke Iwata
Summary: The Thompson score during the first 4 days of life, especially at 72-90 hours, can be useful in predicting short-term adverse outcomes in neonatal encephalopathy. A high Thompson score at 72-90 hours is associated with the need for prolonged life support. However, the rarity of withdrawal of life-sustaining treatment in Japan allows a significant portion of infants with severe encephalopathy and a high Thompson score to recover and survive without tracheostomy.
PEDIATRIC RESEARCH
(2023)
Article
Pediatrics
Kennosuke Tsuda, Jun Shibasaki, Akihito Takeuchi, Takeo Mukai, Yuichiro Sugiyama, Tetsuya Isayama, Tomoaki Ioroi, Akihito Takahashi, Nanae Yutaka, Osuke Iwata, Baby Cooling RegistryJapan
Summary: This study evaluates the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support in newborn infants with hypoxic-ischaemic encephalopathy treated with hypothermia. The study found that prolonged dependence on mechanical ventilation or tube feeding for more than 7 and more than 14 days can predict adverse outcomes at 18 months.
Article
Multidisciplinary Sciences
Masahiro Tsuji, Takeo Mukai, Yoshiaki Sato, Yasue Azuma, Saki Yamamoto, Florence Cayetanot, Laurence Bodineau, Atsuto Onoda, Tokiko Nagamura-Inoue, Jacques-Olivier Coq
Summary: Low birth weight (LBW) increases the risk of neurodevelopmental disorders (NDDs) such as attention-deficit/hyperactive disorder and autism spectrum disorder, and there are currently no prophylactic measures available. Neuroinflammation plays a major role in NDDs, and umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have immunomodulatory properties. This study found that systemic administration of UC-MSCs in the early postnatal period improved hyperexcitability in LBW pups, but the beneficial effects for NDDs were marginal.
SCIENTIFIC REPORTS
(2023)
Article
Pediatrics
Mariko Sekiguchi, Takeo Mukai, Yoshihiko Shitara, Kohei Kashima, Takahiro Seyama, Keiichi Kumasawa, Naoto Takahashi
Summary: Reports on the clinical course of fetal umbilical vein varix in premature infants are limited. We report a case of an extremely low body weight infant with intra-abdominal umbilical vein varix who developed disseminated intravascular coagulation, polycythemia, and hyperbilirubinemia after birth; late-onset neonatal hepatitis; and fetal thrombotic vasculopathy confirmed by placental histopathology. Despite the favorable outcomes reported in the literature, premature infants with umbilical vein varix may require careful observation and management for coagulopathy and late-onset hepatitis.
FRONTIERS IN PEDIATRICS
(2023)
Editorial Material
Pediatrics
Takeo Mukai, Rafael Galindo, Jacques-Olivier Coq
FRONTIERS IN PEDIATRICS
(2023)
Article
Pediatrics
Keisuke Hoshi, Takeo Mukai, Keiichi Kumasawa, Naoto Takahashi
Summary: The patient, a female newborn, had honeycomb-like dilatation and peri-intestinal strong echo patterns in the gastrointestinal tract detected by ultrasonography at 35 weeks and 3 days of gestation. Emergency Cesarean section was performed due to nonreassuring fetal status. After birth, the baby showed hematogenous intragastric residue and defecation, which improved later. Gastrointestinal allergy was suspected and enteral feeding with hydrolyzed protein formula was initiated.
FRONTIERS IN PEDIATRICS
(2023)
Article
Medicine, General & Internal
Takeo Mukai, Kenji Waki
Summary: This article discusses the possibility of XLP in patients with EBV encephalitis and presents a case of a 3-year-old boy diagnosed with XLP. The evaluation revealed mutations in the SH2D1A gene for this patient. The article also mentions the abnormal findings in EEG and head MRI during the patient's admission.
CLINICAL CASE REPORTS
(2023)
Article
Medicine, General & Internal
Takeo Mukai, Kenji Waki
Summary: ALCAPA should be considered as a possible diagnosis in myocarditis, and contrast-enhanced CT or catheterization should be considered even if no coronary artery abnormalities are detected on echocardiography.
CLINICAL CASE REPORTS
(2023)
Article
Obstetrics & Gynecology
Shunichiro Tsuji, Takeo Mukai, Hideaki Tsuchiya, Chizuru Iwatani, Akiko Nakamura, Tokiko Nagamura-Inoue, Takashi Murakami
Summary: This study aimed to investigate the therapeutic potential of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for endometriosis. In a nonhuman primate model, intraperitoneal administration of UC-MSCs exacerbated the condition, while intravenous administration decreased CA125 levels.
REPRODUCTIVE MEDICINE AND BIOLOGY
(2023)
Review
Cell & Tissue Engineering
Makoto Nabetani, Takeo Mukai, Akihiko Taguchi
Summary: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with increased prevalence worldwide. The relationship between ASD and neuroinflammation, microglia, and glucose metabolism has been extensively studied. Cell therapies have shown promising results in clinical studies for ASD treatment, suggesting a new paradigm for autism therapy.
CELL TRANSPLANTATION
(2023)
Article
Biology
Makoto Nabetani, Takeo Mukai
Summary: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impairments in social communication, cognition, motor skills, and executive function. Recent research has focused on the immune pathology in the brains of individuals with ASD, with new therapeutic approaches targeting immune modulation and microglial function. Cell therapies, such as umbilical cord blood cells and mesenchymal stromal cells, show promise as potential treatments for ASD in future clinical studies.
