Wharton’s Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with Hypoxic-Ischemic Encephalopathy

Kabataş, Serdar; Çivelek, Erdinç; İnci, Çiğdem; Yalçınkaya, Ebru Yılmaz; Günel, Gülşen; Kir, Gulay; Albayrak, Esra; Öztürk, Erek; Adaş, Gökhan; Karaöz, Erdal

doi:10.1177/0963689718786692

Cited by 24 publications

(42 citation statements)

References 41 publications

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“…Second, the therapeutic efficacy of the labeled UC-MSCs was not investigated. As the UC-MSCs can be used safely and with minimal ethical complications, they are expected to become the preferred therapeutic stem cell type, especially in neonatal disorders, such as hypoxic-ischemic encephalopathy 46 – 48 . Further studies are necessary to investigate the possibilities of using UC-MSCs in cell-based treatments.…”

Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters

Ohki

Saito

Fukuchi

2020

Sci Rep

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cell tracking with magnetic resonance imaging (MRi) is important for evaluating the biodistribution of transplanted cells. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) have emerged as a promising therapeutic tool in regenerative medicine. We examined the Uc-MScs labeled with superparamagnetic (Spio) and ultrasmall superparamagnetic iron oxide (USpio) in terms of cell functioning and imaging efficiency in vitro and in vivo. The UC-MSCs were co-incubated with SPIO or USPIO at a concentration of 50 or 100 µg/mL of label. Viability and proliferation were assessed by Trypan blue dye exclusion and MTT assay, respectively. Differentiation (chondrogenesis, osteogenesis, and adipogenesis) was induced to examine the impact of labelling on stemness. for in vitro experiments, we used 7-T MRI to assess the T 2 values of phantoms containing various concentrations of cell suspensions. For in vivo experiments, nine neonatal rats were divided into the control, SPIO, and USPIO groups. The UC-MSCs were injected directly into the rat brains. MRI images were obtained immediately and at 7 and 14 days post injection. The UC-MSCs were successfully labeled with SPIO and USPIO after 24 h of incubation. Cell viability was not changed by labelling. Nevertheless, labelling with 100 µg/mL USPIO led to a significant decrease in proliferation. The capacity for differentiation into cartilage was influenced by 100 µg/mL of SPIO. MRI showed that labeled cells exhibited clear hypointense signals, unlike unlabeled control cells. In the USPIO-labeled cells, a significant (P < 0.05) decrease in t 2 values (= improved contrast) was observed when compared with the controls and between phantoms containing the fewest and the most cells (0.5 × 10 6 versus 2.0 × 10 6 cells/mL). In vivo, the labeled cells were discernible on T 2-weighted images at days 0, 7, and 14. The presence of SPIO and USPIO particles at day 14 was confirmed by Prussian blue staining. Microscopy also suggested that the regions occupied by the particles were not as large as the corresponding hypointense areas observed on MRI. Both labels were readily taken up by the UC-MSCs and identified well on MRI. While SPIO and USPIO provide improved results in MRI studies, care must be taken while labelling cells with high concentrations of these agents. Mesenchymal stem cells (MSCs), a kind of somatic stem cells, are isolated from the mesenchymal tissues, such as fat, bone, and cartilage. MSCs can differentiate into mesodermal cells 1 , endodermal 2 , and ectodermal cells 3. Because of their regenerative and immunoregulatory capacities 4 , MSCs are expected to be applied for the therapy of various diseases, such as osteogenesis imperfecta, ischemic stroke, and cardiac infarction. Bone marrow is the most common source of MSCs. However, collecting MSCs from the bone marrow is highly invasive, and the maximal life span of the cells is affected by the donor's age 5. Currently, an umbilical cord tissue called Wharton's jelly is attracting attention, as a promising source of stem cells becaus...

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Section: Discussionmentioning

confidence: 99%

Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters

Ohki

Saito

Fukuchi

2020

Sci Rep

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“…Umbilical cords were obtained from various donors at the Good Manufacturing Practice facility of LivMedCell (Istanbul, Turkey), with informed consents approved by the institutional regulatory board. Postnatal umbilical cords were obtained from donors with full-term pregnancy[ 12 , 13 ].…”

Section: Methodsmentioning

confidence: 99%

“…Multiple-route administration could therefore be a better alternative, with research supporting no side effects by IV and intrathecal (IT) administration[ 10 ]. We previously reported multiple triple-route WJ-MSC administrations to be safe and applicable for HIE and cerebral palsy patients[ 12 , 13 ]. Based on the further research on the matter, WJ-MSCs can now be used for the clinical treatment of HIE.…”

Section: Introductionmentioning

confidence: 99%

Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy

Kabataş¹,

Çivelek²,

Kaplan³

et al. 2021

WJEM

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BACKGROUND Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality. AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients. METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton’s jelly-derived MSCs at 1 × 10 6 /kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes. RESULTS The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month ( P = 0.027) and by 31.38 ± 14.69 in 12 mo ( P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo. CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed.

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“…The cells were characterized by identifying the potential for differentiation using a fl ow cytometer and immunohistochemical analysis, cell aging, cell cycle, annexin V/PI and telomerase enzyme activity at the third passage. The quality control and quality assurance for the production of these cells were conducted in accordance with the standards of the Turkey Pharmaceuticals and Medical Devices Agency (TMMDA) (13).…”

Section: Methodsmentioning

confidence: 99%

Improving effects of mesenchymal stem cells on symptoms of chronic obstructive pulmonary disease

Karaöz¹,

Kalemci²,

Ece³

2020

BLL

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AIM: We aimed to identify the improving effects of umbilical cord tissue-derived (UCTD) MSCs on the symptoms of COPD in our phase 1.2 clinical study. MATERIAL METHODS: Our study consisted of fi ve patients with COPD. Respiratory function tests, SGRQ symptom, activity and impact scores and 6-minute walk test (6MWT) were examined before UCTD MSC treatment. All the patients were administered a total of 4 doses of UCTD MSCs by intravenous infusion at two-week intervals. All the tests were repeated three months after the treatment for evaluation of the response to MSCs treatment. RESULTS: The mean age of fi ve male patients was 56. The mean pretreatment FEV1/FVC ratios were 66.9 %. Pretreatment mean SGRQ symptom, activity and impact scores of the patients were 78.2, 83.8 and 58.02 respectively. The mean walking distance of the patients was 307 meters before MSCs treatment. The mean FEV1/FVC value of raised to 69.58 % after the treatment. The mean SGRQ symptom, activity and impact scores were noted as 39.8, 60.98 and 45.18 respectively. The mean walking distance of the patients raised to 362 meters after the treatment. CONCLUSIONS: Our results showed that four doses of MSC treatment considerably alleviated the severity of symptoms of COPD (Tab. 2, Fig. 7, Ref. 25).

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Wharton’s Jelly-Derived Mesenchymal Stem Cell Transplantation in a Patient with Hypoxic-Ischemic Encephalopathy

Cited by 24 publications

References 41 publications

Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters

Magnetic resonance imaging of umbilical cord stem cells labeled with superparamagnetic iron oxide nanoparticles: effects of labelling and transplantation parameters

Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy

Improving effects of mesenchymal stem cells on symptoms of chronic obstructive pulmonary disease

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