Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain?

Chia, Yvonne Cashinn; Anjum, Clarice Evey; Yee, Hui Rong; Kenisi, Yenny; Chan, Mike Ks; Wong, Michelle Bf; Pan, Shing Yi

doi:10.1155/2020/8889061

Cited by 19 publications

(13 citation statements)

References 83 publications

(103 reference statements)

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“…However, the blood-spinal cord barrier is disrupted for weeks in contusion SCI models [287]. These findings show there is no evidence that stem cells cross the BBB as discussed in a recent review [288]. Early work examined the distribution of stem cells in brain after IV injection, and observed that no stem cells were detected in brain parenchyma, although stem cells invade the meninges of brain [289], where there is no BBB.…”

Section: Stem Cells For Brain Drug Deliverymentioning

confidence: 99%

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A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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The history of brain drug delivery is reviewed beginning with the first demonstration, in 1914, that a drug for syphilis, salvarsan, did not enter the brain, due to the presence of a blood–brain barrier (BBB). Owing to restricted transport across the BBB, FDA-approved drugs for the CNS have been generally limited to lipid-soluble small molecules. Drugs that do not cross the BBB can be re-engineered for transport on endogenous BBB carrier-mediated transport and receptor-mediated transport systems, which were identified during the 1970s–1980s. By the 1990s, a multitude of brain drug delivery technologies emerged, including trans-cranial delivery, CSF delivery, BBB disruption, lipid carriers, prodrugs, stem cells, exosomes, nanoparticles, gene therapy, and biologics. The advantages and limitations of each of these brain drug delivery technologies are critically reviewed.

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Section: Stem Cells For Brain Drug Deliverymentioning

confidence: 99%

“…• Stem cells do not cross the BBB [288], nor enter brain parenchyma [289] as reviewed in Section 5.1.…”

Section: Stem Cell Delivery To Brainmentioning

confidence: 99%

A Historical Review of Brain Drug Delivery

Pardridge

2022

Pharmaceutics

106

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“…It is therefore worthwhile to consider further exploration regarding the use of stem cells as new and effective means to interfere with GWI disease and its progression. It is known that stem cells can successfully home to their target in the brain and initiate repair, making them a promising approach in cellular therapy in neurodegenerative diseases including GWI 20 . Possible sources of self-derived MSC in adult subjects include the bone marrow and fat tissue 18 ; Stem cells from these sources could be used in order to establish their protective effect in vivo in GWI.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Stem Cells from Toxicity Induced by Gulf War Illness (GWI) Serum in N2A Neuroblastoma Cells

Tsilibary¹,

Carlson²,

Georgopoulos³

2021

J Neurol Neuromedicine

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Gulf War Illness (GWI) afflicted many veterans of the 1990-91 Gulf War with multiple symptoms worsening with time. The reasons for GWI have not been elucidated but may include toxicity due to inflammatory factors induced by vaccines administered to deployed and nondeployed veterans. In particular, the anthrax vaccine may have harmful effects in veterans lacking specific protective HLA alleles, as we reported previously, using a murine neuroblastoma N2A cell culture system. Lack of these protective alleles could allow several vaccine antigens to circulate chronically, resulting in protracted low-grade inflammation accompanying the disease. When N2A cells were exposed to GWI serum or the antigen of the anthrax vaccine, the cells underwent apoptosis due to compromised cell membrane, mitochondrial and cytoskeletal function. Elucidation of mechanisms of GWI should provide clues for therapy. Since antigen-induced inflammation accompanies GWI and stem cells were reported to have antimicrobial activity, we examined the effect of murine stem cells co-cultured with N2A cells before exposure to GWI serum and also Protective Antigen PA63, the main component of the anthrax vaccine. The presence of stem cells completely prevented GWI serum toxicity, since it resulted in inhibition of apoptosis. Moreover, cultures of stem cells exposed to PA63 resulted in the degradation of this antigen. We conclude that stem cells can protect against vaccine-induced toxic components of the GWI serum in N2A cells, prompting further studies on the possible beneficial effects of these cells in GWI.

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“…They reduce encephalitis and recover the blood-brain barrier (BBB) in the brain. 56 In gut, they can regulate inflammation, remodel tissue, and promote the eradication of infections (Figure 1). 20 -3 of 14 H7N9) have provided promising hope in the fight against COVID-19.…”

Section: Therapeutic Effects Of Mscsmentioning

confidence: 99%

Mesenchymal stem cells and their derived exosomes to combat Covid–19

dehbidi

Goodarzi

Azhdari

et al. 2021

Reviews in Medical Virology

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Summary Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is causing an ongoing pandemic of coronavirus disease 2019 (Covid‐19). Effective therapies are required for the treatment of patients with severe stages of the disease. Mesenchymal stem cells (MSCs) have been evaluated in numerous clinical trials, but present challenges, such as carcinogenic risk and special storage conditions, coupled with insufficient data about their mechanism of action. The majority of unique properties of MSCs are related to their paracrine activity and especially to their exosomes. The impact of MSCs‐derived exosomes (MSC‐Es) on complications of Covid‐19 has been investigated in several studies. MSC‐Es may improve some complications of Covid‐19 such as cytokine storm, acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Additionally, these exosomes can be evaluated as an applicable nano‐size carrier for antiviral therapeutic agents. Herein, we consider several potential applications of MSCs and their derived exosomes in the treatment of Covid‐19.

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Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain?

Cited by 19 publications

References 83 publications

A Historical Review of Brain Drug Delivery

A Historical Review of Brain Drug Delivery

Protective Effect of Stem Cells from Toxicity Induced by Gulf War Illness (GWI) Serum in N2A Neuroblastoma Cells

Mesenchymal stem cells and their derived exosomes to combat Covid–19

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