Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial
Abstract Neonatal hypoxic ischemic encephalopathy (nHIE) is a serious disease that causes severe and chronic neurological damage. Hypothermia therapy improves patients’ outcomes albeit with some limitations, but combining it with treatment with cord blood cells (analogous to mesenchymal stem cells [...
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-98504-z |
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| author | Kazuko Wada Akihito Takeuchi Yoshinori Katayama Natsuki Ohkawa Masato Kantake Kazumichi Fujioka Toshiya Nishikubo Yutaka Yamamoto Yasumasa Yamada Seiji Yoshimoto Kiyoaki Sumi Tomoaki Ioroi Takeo Mure Norihisa Wada Yukimichi Nakano Naoko Takasao Kenji Tada Tatsuyoshi Yamamoto Hideaki Hirai Yuji Sato Hideyuki Ide Satoshi Kusuda |
| author_facet | Kazuko Wada Akihito Takeuchi Yoshinori Katayama Natsuki Ohkawa Masato Kantake Kazumichi Fujioka Toshiya Nishikubo Yutaka Yamamoto Yasumasa Yamada Seiji Yoshimoto Kiyoaki Sumi Tomoaki Ioroi Takeo Mure Norihisa Wada Yukimichi Nakano Naoko Takasao Kenji Tada Tatsuyoshi Yamamoto Hideaki Hirai Yuji Sato Hideyuki Ide Satoshi Kusuda |
| author_sort | Kazuko Wada |
| collection | DOAJ |
| description | Abstract Neonatal hypoxic ischemic encephalopathy (nHIE) is a serious disease that causes severe and chronic neurological damage. Hypothermia therapy improves patients’ outcomes albeit with some limitations, but combining it with treatment with cord blood cells (analogous to mesenchymal stem cells [MSCs]) reportedly improves its effectiveness. TEMCELL HS Inj. (Temcell), a human bone marrow-derived MSC product used for acute graft-versus-host disease, seems an appropriate candidate for this combination therapy. Therefore, we performed a randomized, parallel-group study to compare combined treatment with Temcell and hypothermia versus hypothermia therapy-alone to evaluate the safety and efficacy of Temcell in nHIE patients. The primary endpoint was treatment response defined as an overall developmental quotient of ≥ 85 at 18 months of age. Fourteen patients were enrolled and randomized, with 7 assigned to each group. Both groups had similar demographic characteristics and nHIE severity. Treatment response was observed in 4 of the 6 (66.7%) patients in the Temcell combination group, and in 4 of the 7 patients (57.1%) in the hypothermia therapy-alone group. No marked differences in safety profile were observed between the groups. These results indicate that the efficacy of Temcell combined with hypothermia is comparable to therapeutic hypothermia for patients with nHIE. Clinical Trial Registration: jRCT1080224818. |
| format | Article |
| id | doaj-art-b5175bcad78e467ca6b78d8b90ec3964 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-b5175bcad78e467ca6b78d8b90ec39642025-08-20T02:15:11ZengNature PortfolioScientific Reports2045-23222025-05-011511810.1038/s41598-025-98504-zCombined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trialKazuko Wada0Akihito Takeuchi1Yoshinori Katayama2Natsuki Ohkawa3Masato Kantake4Kazumichi Fujioka5Toshiya Nishikubo6Yutaka Yamamoto7Yasumasa Yamada8Seiji Yoshimoto9Kiyoaki Sumi10Tomoaki Ioroi11Takeo Mure12Norihisa Wada13Yukimichi Nakano14Naoko Takasao15Kenji Tada16Tatsuyoshi Yamamoto17Hideaki Hirai18Yuji Sato19Hideyuki Ide20Satoshi Kusuda21Department of Neonatal Medicine, Osaka Women’s and Children’s HospitalDivision of Neonatology, NHO Okayama Medical CenterDepartment of Neonatology, Takatsuki General HospitalDepartment of Neonatology, Juntendo University Shizuoka HospitalDivision of Neonatology, Juntendo University Nerima HospitalDepartment of Pediatrics, Kobe University Graduate School of MedicineDivision of Neonatal Intensive Care, Fetal and Neonatal Medical Center, Nara Medical University HospitalDepartment of Neonatology, Gifu Prefectural General Medical CenterDepartment of Perinatal and Neonatal Medicine, Aichi Medical UniversityDepartment of Neonatology, Hyogo Prefectural Kobe Children’s HospitalDepartment of Pediatrics, Aizenbashi HospitalDepartment of Pediatrics, Perinatal Medical Center, Himeji Red Cross HospitalDepartment of Pediatrics, Chibune General HospitalKindai University Hospital Perinatal Medical CenterResearch Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsDevelopment Division, JCR PharmaceuticalsNeonatal Research Network of JapanAbstract Neonatal hypoxic ischemic encephalopathy (nHIE) is a serious disease that causes severe and chronic neurological damage. Hypothermia therapy improves patients’ outcomes albeit with some limitations, but combining it with treatment with cord blood cells (analogous to mesenchymal stem cells [MSCs]) reportedly improves its effectiveness. TEMCELL HS Inj. (Temcell), a human bone marrow-derived MSC product used for acute graft-versus-host disease, seems an appropriate candidate for this combination therapy. Therefore, we performed a randomized, parallel-group study to compare combined treatment with Temcell and hypothermia versus hypothermia therapy-alone to evaluate the safety and efficacy of Temcell in nHIE patients. The primary endpoint was treatment response defined as an overall developmental quotient of ≥ 85 at 18 months of age. Fourteen patients were enrolled and randomized, with 7 assigned to each group. Both groups had similar demographic characteristics and nHIE severity. Treatment response was observed in 4 of the 6 (66.7%) patients in the Temcell combination group, and in 4 of the 7 patients (57.1%) in the hypothermia therapy-alone group. No marked differences in safety profile were observed between the groups. These results indicate that the efficacy of Temcell combined with hypothermia is comparable to therapeutic hypothermia for patients with nHIE. Clinical Trial Registration: jRCT1080224818.https://doi.org/10.1038/s41598-025-98504-z |
| spellingShingle | Kazuko Wada Akihito Takeuchi Yoshinori Katayama Natsuki Ohkawa Masato Kantake Kazumichi Fujioka Toshiya Nishikubo Yutaka Yamamoto Yasumasa Yamada Seiji Yoshimoto Kiyoaki Sumi Tomoaki Ioroi Takeo Mure Norihisa Wada Yukimichi Nakano Naoko Takasao Kenji Tada Tatsuyoshi Yamamoto Hideaki Hirai Yuji Sato Hideyuki Ide Satoshi Kusuda Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial Scientific Reports |
| title | Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial |
| title_full | Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial |
| title_fullStr | Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial |
| title_full_unstemmed | Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial |
| title_short | Combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy: a phase 1/2 randomized trial |
| title_sort | combined treatment with mesenchymal stem cells and therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy a phase 1 2 randomized trial |
| url | https://doi.org/10.1038/s41598-025-98504-z |
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