Advanced Neural Stem Cell Therapies for Spinal Cord Injury

Editorial

06 August 2024

Editorial: Advanced neural stem cell therapies for spinal cord injury

Venkatesh Katari

Santhosh Kumar Pasupuleti

Madhubanti Mullick

Vinod Kumar Reddy Lekkala

and

Dwaipayan Sen

1,065 views

1 citations

Editors

Venkatesh Katari

University of Toledo

Santhosh Kumar Pasupuleti

Department of Pediatrics, Indiana University School of Medicine

Dwaipayan Sen

Stanford University

Impact

Review

27 June 2024

Modern advances in spinal cord regeneration: hydrogel combined with neural stem cells

Oksana Rybachuk

, 1 more and

Valeriia Zhovannyk

2,353 views

2 citations

Functional testing of differentiation and proliferation potential of cell therapy doses. (A) Brightfield images of NES cell doses after 6–7 days in differentiation media. Cells remained viable over the whole time period and displayed increasing neuronal morphology and a higher degree of axonal projections the higher the stage of differentiation. (B) Expression of the markers NESTIN (red) and TUJ1 (green) confirmed by immunocytochemistry. Cropped pictures show zoom-in of relevant region indicated by dotted lines for each picture. Scale bar: 100 μm or 200 μm. (C) Percentage of cells expressing NESTIN and SOX2 as well as TUJ1 when cells from fresh cell culture were compared to thawed batches. Values were comparable between the two conditions fresh vs. frozen cells for all markers. (D) Flowcytometry analysis of NESTIN/SOX2 revealed a continuous loss of NESTIN/SOX2 double positive cells and an increase of (E) TUJ1 positive cells as differentiation progressed. Values left of the dotted line indicate cell doses analyzed directly after thawing and values right of the dotted line indicate progression for doses thawed and differentiated for 7 additional days in vitro. Cells differentiated from NES cells without prior cryopreservation compared to thawed D6 cells appear to exhibit slightly higher levels of differentiation marker TUJ1 expression and a lower proportion of cells double positive for the NES cell markers NESTIN and SOX2. To test if there was in increase in the marker levels the significance was tested between the growth slopes of the curves between the different batches of cells. The slopes were not significantly different between the different batches over the time of differentiation for NESTIN/SOX2 double staining (p > 0.05) while for TUJ1 (E) an exponential growth curve fitted for three out of four batches. These three batches did not differ significantly (p > 0.05) while the fourth one differed significantly from the other three (p = 0.0113). (F) Fold change in cell numbers after doses were cultured in differentiation media for 7 days. An increase in cell numbers was observed for both NES and D3 doses and a decrease in numbers for D6 doses. A regression lines was added between the data points of NES + D7, D3+D7 and D6+D7 for each batch. The slopes between the different regression lines for each batch of cells didn´t differ significantly from each other. A linear regression model was the best fit for this analysis (p > 0.05).

Original Research

22 May 2024

Pre-clinical evaluation of clinically relevant iPS cell derived neuroepithelial stem cells as an off-the-shelf cell therapy for spinal cord injury

Dania Winn

, 3 more and

Anna Falk

1,338 views

0 citations

Small extracellular vesicles – cargo, biogenesis and uptake. The cargo of extracellular vesicles consists of many different biomolecules: lipids, metabolites, nucleic acids (DNA, RNA), and functional proteins including tetraspanins (CD9, CD63, and CD81), cytoskeletal proteins, annexins, proteins participating in membrane transport and fusion (Rab GTPases), heat shock proteins (HSP70 and HSP90), endosomal sorting complex required for transport (ESCRT) proteins that are crucial for vesicle biogenesis, ESCRT complex-related proteins (Tsg101, Alix), major histocompatibility complex (MHC) II and integrins. Vesicle membranes are rich in glycosphingolipids, cholesterol, sphingomyelin and phosphatidylserine. Microvesicles are formed by outward-budding of the plasma membrane and simply released. Exosome biogenesis can be divided into three phases. Invagination of the plasma membrane is followed by formation of multivesicular body (MVBs) by inward budding of the endosomal membrane, followed by exosome release as MVBs fuse with the plasma membrane. Vesicles can be taken up by the recipient cells by either interaction between surface receptors and ligands of vesicles and recipient cell, by direct fusion between vesicle and recipient cell plasma membranes, or by endocytosis.

Review

07 May 2024

The role of small extracellular vesicles and microRNA as their cargo in the spinal cord injury pathophysiology and therapy

Kristyna Sintakova

and

Nataliya Romanyuk

1,977 views

1 citations

Original Research

25 January 2024

A protein–miRNA biomic analysis approach to explore neuroprotective potential of nobiletin in human neural progenitor cells (hNPCs)

Sadaf Jahan

, 10 more and

Aditya Bhushan Pant

Chemical-induced neurotoxicity is increasingly recognized to accelerate the development of neurodegenerative disorders (NDs), which pose an increasing health burden to society. Attempts are being made to develop drugs that can cross the blood–brain barrier and have minimal or no side effects. Nobiletin (NOB), a polymethoxylated flavonoid with anti-oxidative and anti-inflammatory effects, has been demonstrated to be a promising compound to treat a variety of NDs. Here, we investigated the potential role of NOB in sodium arsenate (NA)-induced deregulated miRNAs and target proteins in human neural progenitor cells (hNPCs). The proteomics and microRNA (miRNA) profiling was done for different groups, namely, unexposed control, NA-exposed, NA + NOB, and NOB groups. Following the correlation analysis between deregulated miRNAs and target proteins, RT-PCR analysis was used to validate the selected genes. The proteomic analysis showed that significantly deregulated proteins were associated with neurodegeneration pathways, response to oxidative stress, RNA processing, DNA repair, and apoptotic process following exposure to NA. The OpenArray analysis confirmed that NA exposure significantly altered miRNAs that regulate P53 signaling, Wnt signaling, cell death, and cell cycle pathways. The RT-PCR validation studies concur with proteomic data as marker genes associated with autophagy and apoptosis (HO-1, SQSTM1, LC-3, Cas3, Apaf1, HSP70, and SNCA1) were altered following NA exposure. It was observed that the treatment of NOB significantly restored the deregulated miRNAs and proteins to their basal levels. Hence, it may be considered one of its neuroprotective mechanisms. Together, the findings are promising to demonstrate the potential applicability of NOB as a neuroprotectant against chemical-induced neurotoxicity.

3,780 views

2 citations

Original Research

11 December 2023

Research hotspots and trend analysis of cell transplantation in traumatic spinal cord injury: a bibliometric and visualized analysis

Yuhuai Guo

, 6 more and

Shuo Cai

1,582 views

0 citations

Original Research

18 July 2023

Bibliometric analysis of stem cells for spinal cord injury: current status and emerging frontiers

Zhizhong Shang

, 4 more and

Xin Wang

Background: This study aimed to conduct a bibliometric analysis of the literature on stem cell therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field.

Methods: We searched the Web of Science Core Collection database using relevant keywords (“stem cells” and “spinal cord injury”) and retrieved the published literature between 2000 and 2022. Data such as journal title, author information, institutional affiliation, country, and keywords were extracted. Afterwards, we performed bibliometric analysis of the retrieved data using Bibliometrix, VOSviewer, and CiteSpace.

Results: A total of 5375 articles related to stem cell therapy for spinal cord injury were retrieved, and both the annual publication volume and the cumulative publication volume showed an upward trend. neural regeneration research was the journal with the most publications and the fastest cumulative publication growth (162 articles), Okano Hideyuki was the author with the highest number of publications and citations (114 articles), Sun Yat-sen University was the institution with the highest number of publications (420 articles), and China was the country with the highest number of publications (5357 articles). However, different authors, institutions, and countries need to enhance their cooperation in order to promote the generation of significant academic achievements. Current research in this field has focused on stem cell transplantation, neural regeneration, motor function recovery, exosomes, and tissue engineering. Meanwhile, future research directions are primarily concerned with the molecular mechanisms, safety, clinical trials, exosomes, scaffolds, hydrogels, and inflammatory responses of stem cell therapy for spinal cord injuries.

Conclusion: In summary, this study provided a comprehensive analysis of the current research status and frontiers of stem cell therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of stem cell therapy in this field.

3,523 views

6 citations

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