Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Militello, Guglielmo; Bertolaso, Marta

doi:10.1007/s10441-022-09448-0

Cited by 4 publications

(1 citation statement)

References 124 publications

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“…There are many challenges that hinder cell therapy becoming reality, such as, but not limited to, the selection and purification of stem cells, proliferation and neural differentiation efficiency [11,16,18]. After being transplanted, stem cells face another major obstacle: the cytotoxic microenvironment that is produced by detrimental factors in the host brain and leads to low graft survival of transplants [16,21].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of the Asparaginyl Endopeptidase (AEP) in an Alzheimer’s Disease Model Improves the Survival and Efficacy of Transplanted Neural Stem Cells

Cheng

Liu

et al. 2023

IJMS

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Stem-cell-based therapy is very promising for Alzheimer’s disease (AD), yet has not become a reality. A critical challenge is the transplantation microenvironment, which impacts the therapeutic effect of stem cells. In AD brains, amyloid-beta (Aβ) peptides and inflammatory cytokines continuously poison the tissue microenvironment, leading to low survival of grafted cells and restricted efficacy. It is necessary to create a growth-supporting microenvironment for transplanted cells. Recent advances in AD studies suggest that the asparaginyl endopeptidase (AEP) is a potential intervention target for modifying pathological changes. We here chose APP/PS1 mice as an AD model and employed pharmacological inhibition of the AEP for one month to improve the brain microenvironment. Thereafter, we transplanted neural stem cells (NSCs) into the hippocampus and maintained therapy for one more month. We found that inhibition of AEPs resulted in a significant decrease of Aβ, TNF-α, IL-6 and IL-1β in their brains. In AD mice receiving NSC transplantation alone, the survival of NSCs was at a low level, while in combination with AEP inhibition pre-treatment the survival rate of engrafted cells was doubled. Within the 2-month treatment period, implantation of NSCs plus pre-inhibition of the AEP significantly enhanced neural plasticity of the hippocampus and rescued cognitive impairment. Neither NSC transplantation alone nor AEP inhibition alone achieved significant efficacy. In conclusion, pharmacological inhibition of the AEP ameliorated brain microenvironment of AD mice, and thus improved the survival and therapeutic efficacy of transplanted stem cells.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Inhibition of the Asparaginyl Endopeptidase (AEP) in an Alzheimer’s Disease Model Improves the Survival and Efficacy of Transplanted Neural Stem Cells

Cheng

Liu

et al. 2023

IJMS

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Thinking in 3 dimensions: philosophies of the microenvironment in organoids and organs-on-chip

Caianiello

Bertolaso

Militello

2023

HPLS

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Exosome-bearing hydrogels and cardiac tissue regeneration

Amini,

Namjoo,

Narmi

et al. 2023

Biomater Res

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Background In recent years, cardiovascular disease in particular myocardial infarction (MI) has become the predominant cause of human disability and mortality in the clinical setting. The restricted capacity of adult cardiomyocytes to proliferate and restore the function of infarcted sites is a challenging issue after the occurrence of MI. The application of stem cells and byproducts such as exosomes (Exos) has paved the way for the alleviation of cardiac tissue injury along with conventional medications in clinics. However, the short lifespan and activation of alloreactive immune cells in response to Exos and stem cells are the main issues in patients with MI. Therefore, there is an urgent demand to develop therapeutic approaches with minimum invasion for the restoration of cardiac function. Main body Here, we focused on recent data associated with the application of Exo-loaded hydrogels in ischemic cardiac tissue. Whether and how the advances in tissue engineering modalities have increased the efficiency of whole-based and byproducts (Exos) therapies under ischemic conditions. The integration of nanotechnology and nanobiology for designing novel smart biomaterials with therapeutic outcomes was highlighted. Conclusion Hydrogels can provide suitable platforms for the transfer of Exos, small molecules, drugs, and other bioactive factors for direct injection into the damaged myocardium. Future studies should focus on the improvement of physicochemical properties of Exo-bearing hydrogel to translate for the standard treatment options. Graphical Abstract

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Stem Cells and the Microenvironment: Reciprocity with Asymmetry in Regenerative Medicine

Cited by 4 publications

References 124 publications

Pharmacological Inhibition of the Asparaginyl Endopeptidase (AEP) in an Alzheimer’s Disease Model Improves the Survival and Efficacy of Transplanted Neural Stem Cells

Pharmacological Inhibition of the Asparaginyl Endopeptidase (AEP) in an Alzheimer’s Disease Model Improves the Survival and Efficacy of Transplanted Neural Stem Cells

Thinking in 3 dimensions: philosophies of the microenvironment in organoids and organs-on-chip

Exosome-bearing hydrogels and cardiac tissue regeneration

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