Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia

Akhlaghpasand, Mohammadhosein; Tizro, Mahdi; Raoofi, Amir; Meymand, Arman Zeinaddini; Farhadieh, Mohammaderfan; Khodagholi, Fariba; Khatmi, Aysan; Soltani, Reza; Hoseini, Yadolah; Jahanian, Ali; Boroujeni, Mahdi Eskandarian; Aliaghaei, Abbas

doi:10.1007/s11011-020-00543-0

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…It has been observed that both amniotic mesenchymal cells and chorionic mesenchymal cells have an immunomodulatory effect and can prevent graft rejection and inflammatory response 34 – 36 . Furthermore, it has been suggested that the mesenchymal cells of the amnion have pro-angiogenic abilities and can promote angiogenesis after implantation 37 – 39 . Moreover, amniotic mesenchymal cells contain various angiogenic growth factors, including angiopoietin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) 40 , 41 .…”

Section: Discussionmentioning

confidence: 99%

Developing a pro-angiogenic placenta derived amniochorionic scaffold with two exposed basement membranes as substrates for cultivating endothelial cells

Shariatzadeh

Shafiee

Zafari

et al. 2021

Sci Rep

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Decellularized and de-epithelialized placenta membranes have widely been used as scaffolds and grafts in tissue engineering and regenerative medicine. Exceptional pro-angiogenic and biomechanical properties and low immunogenicity have made the amniochorionic membrane a unique substrate which provides an enriched niche for cellular growth. Herein, an optimized combination of enzymatic solutions (based on streptokinase) with mechanical scrapping is used to remove the amniotic epithelium and chorion trophoblastic layer, which resulted in exposing the basement membranes of both sides without their separation and subsequent damages to the in-between spongy layer. Biomechanical and biodegradability properties, endothelial proliferation capacity, and in vivo pro-angiogenic capabilities of the substrate were also evaluated. Histological staining, immunohistochemistry (IHC) staining for collagen IV, and scanning electron microscope demonstrated that the underlying amniotic and chorionic basement membranes remained intact while the epithelial and trophoblastic layers were entirely removed without considerable damage to basement membranes. The biomechanical evaluation showed that the scaffold is suturable. Proliferation assay, real-time polymerase chain reaction for endothelial adhesion molecules, and IHC demonstrated that both side basement membranes could support the growth of endothelial cells without altering endothelial characteristics. The dorsal skinfold chamber animal model indicated that both side basement membranes could promote angiogenesis. This bi-sided substrate with two exposed surfaces for cultivating various cells would have potential applications in the skin, cardiac, vascularized composite allografts, and microvascular tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Developing a pro-angiogenic placenta derived amniochorionic scaffold with two exposed basement membranes as substrates for cultivating endothelial cells

Shariatzadeh

Shafiee

Zafari

et al. 2021

Sci Rep

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“…Stem cell therapies for neurologic disease have had suggested mechanisms that range from neural replacement to nerve growth factor enhancement to use as a delivery vehicle for other therapy [40][41][42]. A phase 1/2a open-label study of intravenous adipose-derived mesenchymal stem cell treatment in 6 patients with spinocerebellar ataxia type 3 (ClinicalTrials.gov Identifier: NCT01649687) demonstrated good safety and tolerability over 1 year with plans to conduct a larger, controlled trial in the future [43].…”

Section: Neural Replacementmentioning

confidence: 99%

Update on the Treatment of Ataxia: Medication and Emerging Therapies

Perlman

2020

Neurotherapeutics

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While rehabilitation therapies always help patients with ataxia, there are currently no FDA-approved treatments for ataxia. Medications are available to treat symptoms that may complicate an ataxic illness, e.g., tremor, myoclonus, dystonia, and rigidity, which are discussed elsewhere in this volume. Spasticity, pain, fatigue, depression, sleep disturbances, cognitive decline, and bowel and bladder dysfunction, if they occur, all have multiple available drugs and therapies for symptomatic use. There is also an extensive literature on off-label uses of various medications to improve imbalance. The pipeline of emerging therapies for symptomatic and possible disease-modifying management of ataxia gives hope that we will soon see the first of many FDAapproved drugs for ataxic illnesses.

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“…Purkinje cell degeneration is an inherited or sporadic disease characterized by progressive gait and coordination disorders 4,5,6 . Although immunotherapy 7 , electrical stimulation 8 , gene therapy 9,10 , stem cell transplantation 11,12,13 and other means have been studied to treat animal models of neurodegenerative diseases, the curative effect is not ideal. Chronic mitochondrial dysfunction accompanied by biological energy depletion is a pathological marker of major neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Brain injury triggers acute mitochondrial damage and a local energy crisis that accelerates neuronal death. Defective mitochondrial maintenance and insu cient axon energy have become central problems in neurodegenerative diseases and brain injuries 13 . Alterations in mitochondrial DNA have been described in diseases, including deletions, point mutations, depletion, and maintenance alterations.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria transfer transiently rescues cerebellar neurodegeneration at early stage by alleviating mitophagy

Wang,

Li,

Zheng

et al. 2024

Preprint

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Cerebellar ataxia is the main manifestation of cerebellar degenerative diseases, and the mitochondrial function of Purkinje cells (PCs) plays a key role in the disease. And treatments targeting the cerebellum need further research. We constructed a model of cerebellar PCs degeneration, characterized by ataxia, through conditional knockout of Drp1 in PCs (PCKO mice). And we further explored the pathogenesis and possible effective treatment of cerebellar degenerative diseases. Drp1 knockout results in pervasive and progressive apoptosis of PCs, accompanied by severe glial cell activation surrounding them. Mitochondrial dysfunction, as a cause of mitophagy, is a key pathogenic factor of PCs morphological damage and dysfunction. Transfer of liver-derived mitochondria into the cerebellum of PCKO mice at 1 month improved mitochondrial function and reduced mitophagy, resulting in a delay of PCs apoptosis and cerebellar ataxia for 3 weeks. This study demonstrates that mitochondria transfer may be an potential treatment for cerebellar degenerative diseases.

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Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia

Cited by 6 publications

References 46 publications

Developing a pro-angiogenic placenta derived amniochorionic scaffold with two exposed basement membranes as substrates for cultivating endothelial cells

Developing a pro-angiogenic placenta derived amniochorionic scaffold with two exposed basement membranes as substrates for cultivating endothelial cells

Update on the Treatment of Ataxia: Medication and Emerging Therapies

Mitochondria transfer transiently rescues cerebellar neurodegeneration at early stage by alleviating mitophagy

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