Annotated Literature Review (3)

Mireya Ibanez

March 7, 2021

BME 295C

Ms. Barton

Annotated Literature Review:

1. Mesenchymal Stem Cells in the Treatment of Traumatic Brain Injury.Hasan A, Deeb G, Rahal R, Atwi K, Mondello S, Marei HE, Gali A, Sleiman E.

Front Neurol. 2017 Feb 20;8:28. doi: 10.3389/fneur.2017.00028. eCollection 2017.

PMID: 28265255 

The review introduces the use of the Mesenchymal stem cells in Traumatic Brain injury. Studies have shown that using a MSC approach can be a treatment to patients who have a TBI. One study conducted by Cox involved implanting Mesenchymal stem cells into 10 children. The results showed improvement for 7, and no significant result on the remaining children. The most effective result reoccurred the sooner the patient received the Mesenchymal stem cells. MSC is growing to be an enormous opportunity for helping people post- TBI repair.

2. Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury.Willing AE, Das M, Howell M, Mohapatra SS, Mohapatra S.

CNS Neurosci Ther. 2020 Jun;26(6):616-627. doi: 10.1111/cns.13300. Epub 2020 Mar 10.

PMID: 32157822 

Mesenchymal stem cell therapy has been showing promising results in ongoing clinical studies. There is different therapeutic approaches for a Traumatic Brain Injury in combination with clinical Mesenchymal stem cell trials. The clinical trials have at least entered the beginning stages (safety phases) for multiple diseases and injuries including TBI’s. Researchers have been able to get a better understanding of what occurs to the body after sustaining a TBI and how Mesenchymal stem cells repairs the brain and improves functional outcomes. A lot of research and clinical trials is still needed to be able to create an effective therapy for patients suffering from Traumatic Brain injury.

3. Systemic administration of cell-free exosomes generated by human bone marrow derived mesenchymal stem cells cultured under 2D and 3D conditions improves functional recovery in rats after traumatic brain injury.Zhang Y, Chopp M, Zhang ZG, Katakowski M, Xin H, Qu C, Ali M, Mahmood A, Xiong Y.

Neurochem Int. 2017 Dec;111:69-81. doi: 10.1016/j.neuint.2016.08.003. Epub 2016 Aug 15.

PMID: 27539657 

A study has been conducted to see if the administration of cell-free exosomes derived from h-Mesenchymal stem cells can promote functional recovery and neurovascular remodeling in rats after a Traumatic Brain injury. Wistar rats were tested by giving them an induced TBI and 24 hours later injecting them with the exosomes. The exosomes treatment significantly improved functional recovery in rats after obtaining a Traumatic Brain injury. The results included promoting endogenous angiogenesis and neurogenesis and reducing inflammation. hMSCs have the potential to be a cell-free therapy for a TBI and exosomes can possibly enhance spatial learning.

4. Human adipose-derived mesenchymal stem cells for acute and sub-acute TBI.Ruppert KA, Prabhakara KS, Toledano-Furman NE, Udtha S, Arceneaux AQ, Park H, Dao A, Cox CS, Olson SD.

PLoS One. 2020 May 26;15(5):e0233263. doi: 10.1371/journal.pone.0233263. eCollection 2020.

PMID: 32453741 

There are many attempts of intervention focusing on protection and, repair or regeneration when traumatic brain injury occurs. The use of stem cells from a variety of sources and applications has been studied in many disease and injury models. This study involves administering h-Mesenchymal stem cells into a rat. The earliest administration at 3 days after and delayed administration 14 days after a controlled cortical impact injury. The treatments show improvements in neurocognitive outcome and a change in the neuroinflammation one month after the injury. There is significant data and results that support the idea of using adMSC to treat a TBI. There is still ongoing research to find the optimal time to administrate the therapy to have the most successful results.

5. Bone marrow mesenchymal stem cells combined with Sox2 increase the functional recovery in rat with traumatic brain injury.Hao Q, Zheng J, Hu Y, Wang H.

Chin Neurosurg J. 2019 May 15;5:11. doi: 10.1186/s41016-019-0158-7. eCollection 2019.

PMID: 32922911 

In many studies, it is found that the stem cell transplantation holds potential results for modifying motor dysfunctions caused by Traumatic Brain injuries. 26 rats were used in a study, with 2 rats being bone marrow stem cell donors. 2 days after a Traumatic Brain injury, the rats were induced with SOX-2 and the study examined the effects of SOX-2 with the differentiation of bsMSCs. The motor function was tested using NSS. (Neurological severity score) The study showed there was neurological function improvements. This treatment is another step to creating a promising therapy for Traumatic Brain Injuries.

6. Transplantation of R-GSIK scaffold with mesenchymal stem cells improves neuroinflammation in a traumatic brain injury model.Sahab Negah S, Shirzad MM, Biglari G, Naseri F, Hosseini Ravandi H, Hassani Dooghabadi A, Gorji A.

Cell Tissue Res. 2020 Dec;382(3):575-583. doi: 10.1007/s00441-020-03247-0. Epub 2020 Jul 27.

PMID: 32715374 

Neural tissue engineering has been introduced by using Mesenchymal stem cells and R-GSIK to provide a therapeutic strategy for a Traumatic Brain injury. The study was designed to promote the behavior of the stem cells by incorporating R-GSIK in rats. There was significant recovery of motor function observed in the rats that received Mesenchymal stem cells and R-GSIK. Compared to other control groups there was a reduction in pro-inflammatory cytokines. This helped to strengthen the idea that R-GSIK and Mesenchymal stem cells are a step in helping patients who suffer from a Traumatic Brain injury.

7. Transplantation of mesenchymal stem cells genetically engineered to overexpress interleukin-10 promotes alternative inflammatory response in rat model of traumatic brain injury.Peruzzaro ST, Andrews MMM, Al-Gharaibeh A, Pupiec O, Resk M, Story D, Maiti P, Rossignol J, Dunbar GL.

J Neuroinflammation. 2019 Jan 5;16(1):2. doi: 10.1186/s12974-018-1383-2.

PMID: 30611291 

Traumatic Brain injury are major causes to long term disability with a limit on the treatments available. In order to see responses of the methods, researchers look at the Neuroinflammatory responses. One specific method involves transplantation of Mesenchymal stem cells. These Mesenchymal stem cells release trophic and pro-repair cytokine, specifically interleukin10. The study tests the therapeutic effects when transplanted into rats that endured a Traumatic brain injury in the frontal cortex. There were significant improvements to reduce inflammation and promote functional outcomes, although further testing and research needs to be conducted. This could be very good in human research, if the rats continue to show good results.

8. Treating childhood traumatic brain injury with autologous stem cell therapy.Dewan S, Schimmel S, Borlongan CV.

Expert Opin Biol Ther. 2018 May;18(5):515-524. doi: 10.1080/14712598.2018.1439473. Epub 2018 Feb 15.

PMID: 29421958 

A significant contributor to developmental disorders occurs from childhood related Traumatic Brain Injuries. Stem cell therapy, meaning using stem cells from the own individual is a believed therapy to enhance the repair of the injured neonatal brain. The use of autologous stem cells can delay ad possibly stop the neuroinflammation that causes cell death to occur. This therapy has very promising potential to treating neuroinflammation related with acute and progressive stages of neonatal Traumatic brain injury. There is a bunch of room of new information that can help the therapy, such as introducing new components to ensure a good outcome.