Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Gong, Yuhua; Hao, Shilei; Wang, Bochu

doi:10.3389/fncel.2021.653367

Cited by 12 publications

(8 citation statements)

References 107 publications

(138 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ICH promotes cellular damage, including cytotoxicity and oxidative stress in blood released from blood vessels as well as in ammation [55] Consistent with our data (Fig. 6), apoptosis has been observed in the ICH lesion [29].…”

Section: Discussionsupporting

confidence: 91%

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Kuramoto

Fujita

Takagi

et al. 2021

Preprint

View full text Add to dashboard Cite

Background Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts. Methods hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a 10-fold higher dose of hADSCs were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment. Results The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages. In details, the hAMSC treatment decreased the number of CD11b+CD45+ and Ly6G+ cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα. Conclusions Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.

show abstract

Section: Discussionsupporting

confidence: 91%

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Kuramoto

Fujita

Takagi

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…ICH promotes cellular damage, including cytotoxicity and oxidative stress in blood released from blood vessels as well as inflammation [ 56 ] Consistent with our data (Fig. 6 ), apoptosis has been observed in the ICH lesion [ 30 ].…”

Section: Discussionsupporting

confidence: 89%

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Kuramoto

Fujita

Takagi

et al. 2022

J Neuroinflammation

View full text Add to dashboard Cite

Background Intracerebral hemorrhage (ICH) is a significant cause of death and disabilities. Recently, cell therapies using mesenchymal stem cells have been shown to improve ICH-induced neurobehavioral deficits. Based on these findings, we designed this study to evaluate the therapeutic efficacy and underlying mechanisms by which human amnion-derived stem cells (hAMSCs) would ameliorate neurobehavioral deficits of ICH-bearing hosts. Methods hAMSCs were induced from amnia obtained by cesarean section and administered intravenously to ICH-bearing mice during the acute phase. The mice were then subject to multitask neurobehavioral tests at the subacute phase. We attempted to optimize the dosage and timing of the hAMSC administrations. In parallel with the hAMSCs, a tenfold higher dose of human adipose-derived stem cells (ADSCs) were used as an experimental control. Specimens were obtained from the ICH lesions to conduct immunostaining, flow cytometry, and Western blotting to elucidate the underlying mechanisms of the hAMSC treatment. Results The intravenous administration of hAMSCs to the ICH-bearing mice effectively improved their neurobehavioral deficits, particularly when the treatment was initiated at Day 1 after the ICH induction. Of note, the hAMSCs promoted clinical efficacy equivalent to or better than that of hADSCs at 1/10 the cell number. The systemically administered hAMSCs were found in the ICH lesions along with the local accumulation of macrophages/microglia. In detail, the hAMSC treatment decreased the number of CD11b+CD45+ and Ly6G+ cells in the ICH lesions, while splenocytes were not affected. Moreover, the hAMSC treatment decreased the number of apoptotic cells in the ICH lesions. These results were associated with suppression of the protein expression levels of macrophage-related factors iNOS and TNFα. Conclusions Intravenous hAMSC administration during the acute phase would improve ICH-induced neurobehavioral disorders. The underlying mechanism was suggested to be the suppression of subacute inflammation and apoptosis by suppressing macrophage/microglia cell numbers and macrophage functions (such as TNFα and iNOS). From a clinical point of view, hAMSC-based treatment may be a novel strategy for the treatment of ICH.

show abstract

“…Some studies have verified that MSCs can be isolated from various adult tissues such as the bone marrow, adipose tissue, synovium, and neonatal tissues, including the umbilical cord (blood), placenta, amniotic fluid, and amniotic membrane, and possess the potential of differentiating into diverse cell lineages and tissues like bone, adipose tissue, cartilage, nerves, and liver, both in vivo and in vitro ( Gao et al, 2018 ; Sumer et al, 2018 ; Mathot et al, 2019 ; Gong et al, 2021 ; Li J. et al, 2021 ; Li Q. Y. et al, 2021 ; Ramesh et al, 2021 ; Souza et al, 2021 ; Zhu et al, 2021 ; Bian et al, 2022 ). Others have verified that MSC treatment holding promise exerts indirect therapeutic mechanisms such as anti-inflammation ( Huang et al, 2019 ), secretion of growth factors ( Tang W. et al, 2021 ; Ulpiano et al, 2021 ), and EVs ( Bang and Kim, 2022 ), which are associated with the recovery of damaged tissues.…”

Section: Different Sources Of Mesenchymal Stem Cells In Intracerebral...mentioning

confidence: 99%

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

Yang

Fan

Mazhar

et al. 2022

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH), a common lethal subtype of stroke accounting for nearly 10–15% of the total stroke disease and affecting two million people worldwide, has a high mortality and disability rate and, thus, a major socioeconomic burden. However, there is no effective treatment available currently. The role of mesenchymal stem cells (MSCs) in regenerative medicine is well known owing to the simplicity of acquisition from various sources, low immunogenicity, adaptation to the autogenic and allogeneic systems, immunomodulation, self-recovery by secreting extracellular vesicles (EVs), regenerative repair, and antioxidative stress. MSC therapy provides an increasingly attractive therapeutic approach for ICH. Recently, the functions of MSCs such as neuroprotection, anti-inflammation, and improvement in synaptic plasticity have been widely researched in human and rodent models of ICH. MSC transplantation has been proven to improve ICH-induced injury, including the damage of nerve cells and oligodendrocytes, the activation of microglia and astrocytes, and the destruction of blood vessels. The improvement and recovery of neurological functions in rodent ICH models were demonstrated via the mechanisms such as neurogenesis, angiogenesis, anti-inflammation, anti-apoptosis, and synaptic plasticity. Here, we discuss the pathological mechanisms following ICH and the therapeutic mechanisms of MSC-based therapy to unravel new cues for future therapeutic strategies. Furthermore, some potential strategies for enhancing the therapeutic function of MSC transplantation have also been suggested.

show abstract

Mesenchymal Stem Cells Transplantation in Intracerebral Hemorrhage: Application and Challenges

Cited by 12 publications

References 107 publications

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Early-phase administration of human amnion-derived stem cells ameliorates neurobehavioral deficits of intracerebral hemorrhage by suppressing local inflammation and apoptosis

Mesenchymal Stem Cell Application and Its Therapeutic Mechanisms in Intracerebral Hemorrhage

Contact Info

Product

Resources

About