Prodigious therapeutic effects of combining mesenchymal stem cells with magnetic nanoparticles

BACKGROUND Mesenchymal stem cells (MSCs) have been extensively studied for therapeutic potential, due to their regenerative and immunomodulatory properties. Serial passage and stress factors may affect the biological characteristics of MSCs, but the details of these effects have not been recognized yet. AIM To investigate the effects of stress factors (high glucose and severe hypoxia) on the biological characteristics of MSCs at different passages, in order to optimize the therapeutic applications of MSCs. METHODS In this study, we investigated the impact of two stress conditions; severe hypoxia and high glucose on human adipose-tissue derived MSCs (hAD-MSCs) at passages 6 (P6), P8, and P10. Proliferation, senescence and apoptosis were evaluated measuring WST-1, senescence-associated beta-galactosidase, and annexin V, respectively. RESULTS Cells at P6 showed decreased proliferation and increased apoptosis under conditions of high glucose and hypoxia compared to control, while the extent of senescence did not change significantly under stress conditions. At P8 hAD-MSCs cultured in stress conditions had a significant decrease in proliferation and apoptosis and a significant increase in senescence compared to counterpart cells at P6. Cells cultured in high glucose at P10 had lower proliferation and higher senescence than their counterparts in the previous passage, while no change in apoptosis was observed. On the other hand, MSCs cultured under hypoxia showed decreased senescence, increased apoptosis and no significant change in proliferation when compared to the same conditions at P8. CONCLUSION These results indicate that stress factors had distinct effects on the biological processes of MSCs at different passages, and suggest that senescence may be a protective mechanism for MSCs to survive under stress conditions at higher passage numbers.

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of high glucose and severe hypoxia on the biological behavior of mesenchymal stem cells at various passages

Almahasneh,

Abu-El-Rub,

Khasawneh

et al. 2024

“…Continuing their efforts to study the effects of hyperglycemia on MSC functionality, Abu-El-Rub et al [ 20 ] reported interesting comparative data in vitro by culturing human adipose tissue-derived MSCs (AD-MSCs) under low glucose and HG conditions in a parallel set of experiments. It is pertinent to mention that the authors used in vitro culture conditions for exposure to HG.…”

Section: Hg Culture- and Hyperglycemia-induced Signalingmentioning

confidence: 99%

“…Endoplasmic reticulum stress-induced autophagy is another mechanism contributing to the inactivation of mTOR, which was shown to reduce p-S6 (a marker of mTOR activity)[ 23 ]. Building on these data, Abu-El-Rub et al [ 20 ] revealed higher apoptosis in human AD-MSCs (hAD-MSCs) cultured in HG using low glucose culture as the control. Elucidating the mechanism causing poor survival of MSCs in an HG microenvironment via impairment of the phosphoinositide 3-kinase (PI3K)/mTOR axis, they found significantly increased tuberous sclerosis 1 (TSC1) protein.…”

Section: Cell Viability and Apoptosismentioning

confidence: 99%

High glucose microenvironment and human mesenchymal stem cell behavior

Mateen,

Alaagib,

Haider

2024

High glucose (HG) culture conditions in vitro and persistent exposure to hyperglycemia in diabetes patients are detrimental to stem cells, analogous to any other cell type in our body. It interferes with diverse signaling pathways, i.e. mammalian target of rapamycin (mTOR)-phosphoinositide 3-kinase (PI3K)-Akt signaling, to impact physiological cellular functions, leading to low cell survival and higher cell apoptosis rates. While elucidating the underlying mechanism responsible for the apoptosis of adipose tissue-derived mesenchymal stem cells (MSCs), a recent study has shown that HG culture conditions dysregulate mTOR-PI3K-Akt signaling in addition to mitochondrial malfunctioning due to defective mitochondrial membrane potential (MtMP) that lowers ATP production. This organelle-level dysfunction energy-starves the cells and increases oxidative stress and ultrastructural abnormalities. Disruption of the mitochondrial electron transport chain produces an altered mitochondrial NAD+/NADH redox state as evidenced by a low NAD+/NADH ratio that primarily contributes to the reduced cell survival in HG. Some previous studies have also reported altered mitochondrial membrane polarity (causing hyperpolarization) and reduced mitochondrial cell mass, leading to perturbed mitochondrial homeostasis. The hostile microenvironment created by HG exposure creates structural and functional changes in the mitochondria, altering their bioenergetics and reducing their capacity to produce ATP. These are significant data, as MSCs are extensively studied for tissue regeneration and restoring their normal functioning in cell-based therapy. Therefore, MSCs from hyperglycemic donors should be cautiously used in clinical settings for cell-based therapy due to concerns of their poor survival rates and increased rates of post engraftment proliferation. As hyperglycemia alters the bioenergetics of donor MSCs, rectifying the loss of MtMP may be an excellent target for future research to restore the normal functioning of MSCs in hyperglycemic patients.

“…Using artificial intelligence in stem cell research introduces a new set of challenges mostly related to ethical considerations, policy implications, and intellectual property, demanding a risk-based approach to balance the potential benefits and risks. Abu-El-Rub et al [ 16 ] discussed one important aspect of MSC transplantation within the survival-challenging environment of diabetes mellitus (DM) patients. MSC transplantation has been proposed as a potential treatment for type I and II DM mainly due to its immunosuppressive properties and anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

Understanding host-graft crosstalk for predicting the outcome of stem cell transplantation

Labusca,

Zugun-Eloae

2024

Mesenchymal stromal cells (MSCs) hold great promise for tissue regeneration in debilitating disorders. Despite reported improvements, the short-term outcomes of MSC transplantation, which is possibly linked to poor cell survival, demand extensive investigation. Disease-associated stress microenvironments further complicate outcomes. This debate underscores the need for a deeper understanding of the phenotypes of transplanted MSCs and their environment-induced fluctuations. Additionally, questions arise about how to predict, track, and comprehend cell fate post-transplantation. In vivo cellular imaging has emerged as a critical requirement for both short- and long-term safety and efficacy studies. However, translating preclinical imaging methods to clinical settings remains challenging. The fate and function of transplanted cells within the host environment present intricate challenges, including MSC engraftment, variability, and inconsistencies between preclinical and clinical data. The study explored the impact of high glucose concentrations on MSC survival in diabetic environments, emphasizing mitochondrial factors. Preserving these factors may enhance MSC survival, suggesting potential strategies involving genetic modification, biomaterials, and nanoparticles. Understanding stressors in diabetic patients is crucial for predicting the effects of MSC-based therapies. These multifaceted challenges call for a holistic approach involving the incorporation of large-scale data, computational disease modeling, and possibly artificial intelligence to enable deterministic insights.