Biology subjects

Herrera-Lopez, G.

Publications and source records attributed to Herrera-Lopez, G..

3 recordsLinked to original sources

bioRxiv2026

Establishment of the Saudi Bank of Induced Pluripotent Stem Cells (SBiPSCs): A National Platform for iPSC-Based Research and Therapy

BackgroundThe global landscape of induced pluripotent stem cell (iPSC) resources remains heavily skewed toward European, North American, and East Asian populations, leaving the Middle East and North Africa (MENA) region critically underrepresented. This disparity hinders the application of precision medicine in populations with unique genetic backgrounds, particularly those with high rates of consanguinity and distinctive rare disease profiles. To address this gap, we established the Saudi Bank of Induced Pluripotent Stem Cells (SBiPSCs), at King Abdullah International Medical Research Centre (KAIMRC). The bank comprises two major complementary arms: one dedicated to the derivation and biobanking of iPSCs from individuals with rare and common genetic disorders, and a second focused on Human Leukocyte Antigen (HLA)-based iPSC banking to support the development of immunocompatible cell therapies. MethodsSBiPSCs operates within King Abdulaziz Medical City in Jeddah under the Ministry of National Guard for Health Affairs (MNGHA)s ethical and clinical framework. To establish the repository, we implemented a clinic-guided enrolment strategy in which treating physicians, briefed on the banks objectives, recruited patients with confirmed genetic diagnoses. Peripheral blood samples were collected, processed, and cells were reprogrammed using non-integrating episomal plasmids. All derived lines underwent rigorous quality control in accordance with International Society for Stem Cell Research (ISSCR) standards, including assessment of pluripotency markers, genomic integrity, and trilineage differentiation potential. To demonstrate our iPS characterization workflow and translational utility, iPSCs from a Saudi patient with familial Long QT Syndrome (LQTS) and a healthy sibling were differentiated into functional cardiac organoids. Simultaneously, for the HLA-based banking arm, the Saudi Stem Cell Donor Registry (SSCDR) database was leveraged to identify donors predicted to provide maximal coverage for the Saudi population. ResultsTo date, SBiPSCs has successfully generated 37 iPSC lines derived from 19 Saudi patients and healthy donors. All lines exhibit robust expression of pluripotency markers, maintain normal karyotypes, and demonstrate differentiation capacity. To demonstrate our characterization pipeline and translational utility, iPSCs from an LQTS patient and a healthy sibling were generated, validated, and differentiated into beating cardiac organoids that recapitulated the disease phenotype, with microelectrode array analysis confirming prolonged field potential durations mirroring the clinical QT prolongation. Furthermore, the HLA-based banking arm has expanded to include two homozygous iPSC lines, which together provide immunological compatibility for approximately 9% of the Saudi population. ConclusionsSBiPSCs represents the first centralized iPSC repository in the MENA region. The SBiPSCs is well-positioned to accelerate the translation of stem cell research into scalable, immunocompatible cell therapies and precision medicine applications aligned with national and regional healthcare priorities.

genetics↗

bioRxiv2024

Lactate potentiates NMDA receptor currents via an intracellular redox mechanism targeting cysteines in the C-terminal domain of GluN2B subunits: implications for synaptic plasticity

SummaryThrough the Astrocyte Neuron Lactate Shuttle, astrocyte-derived lactate fuels the high-energy demands of neurons and acts as a signaling molecule, promoting synaptic plasticity and memory consolidation. Lactate regulates neuronal excitability and modulates the expression of genes related to synaptic plasticity and neuroprotection, but the molecular mode for these signaling actions is uncertain. Using patch-clamp recordings in cultured cortical neurons, we found that lactate enhances both the amplitude and the inactivation time constant of NMDA receptor currents (INMDAR) evoked by brief applications of glutamate and glycine. Not reproduced by HCAR1 agonists, this modulation depends on monocarboxylate transporters and lactate dehydrogenase, indicating the requirement for lactate entry and metabolic conversion into pyruvate and NADH formation within neurons. Disruption of intracellular calcium dynamics or inhibition of Ca2+/calmodulin-dependent protein kinase II (CaMKII), a NMDAR-associated kinase linking Ca2+ signal to long-term potentiation (LTP), significantly diminishes the effects of lactate on INMDAR. We identified two redox-sensitive cysteine- containing sequences in the intrinsically disordered intracellular C-terminal domain of the GluN2B subunit that play a role in the potentiation of NMDAR by lactate. In a compelling set of experiments using HEK cells, we observed that the presence of functional CaMKII and GluN2B-containing NMDARs is necessary for the lactate-enhancing effects. Mutations in GluN2B that prevent CaMKII binding or redox regulation via cysteines abrogate the modulatory action of lactate. Immunoprecipitation experiments in neurons attest that lactate increases the association between CaMKII and GluN2B. This interaction is crucial for the potentiation of INMDAR amplitude by lactate. Proximity ligation assays between GluN2B and the postsynaptic density marker PSD-95 revealed that lactate induced an accumulation of GluN2B in dendritic spines, an effect that was prevented by a CaMKII peptide inhibitor. These results highlight a mechanistic pathway whereby lactate boosts NMDAR function through intracellular metabolic conversion and redox-sensitive interactions requiring CaMKII, establishing a link between astrocyte metabolism and synaptic modulation in neurons.

neuroscience↗

bioRxiv2022

Photo-electrochemical Stimulation of Neurons With Organic Donor-Acceptor Heterojunctions

Recent advancements in light-responsive materials enabled the development of devices to artificially activate tissue with light, and show great potential for use in different types of therapy. Photo-stimulation based on organic semiconductors has recently attracted interest due to their unique set of properties such as biocompatibility, better mechanical match with human tissue, and strong absorption of light in the visible spectrum. Here we show the development of solution processed organic heterojunctions that are able to control the activity of primary neurons in vitro with light. The p-type polymer semiconductor PDCBT and the n-type polymer semiconductor ITIC (also known as non-fullerene acceptor) are simply spin coated on glass substrates forming a bilayer p-n junction with high photo-sensitivity in aqueous electrolytes. Photo-electrochemical measurements reveal that high photo-voltage and photo-current is produced, as a result of a charge transfer between the polymers and oxygen in the electrolyte. The biocompatibility of the proposed materials is addressed with live/dead assays on both primary mouse cortical neurons and human cell lines that are cultured on their surface. We have found that light of low intensity (i.e. 40 mW/cm2) is absorbed, and converted into a cue that triggers action potential on primary cortical neurons directly cultured on glass/PDCBT/ITIC interfaces as proven by patch clamp measurements. The activation of neurons is most likely due to photochemical reactions at the polymer/electrolyte interface that result in hydrogen peroxide, which might lead to modulation of specific ion channels on neurons membrane. Photo-thermal effects are excluded with controlled patch clamp measurements on neurons cultured on plain glass and on photoresist thin films. The profound advantages of low intensity light stimulation, simplified fabrication, and wireless operation pave the way for the integration of these interfaces in multiplex bioelectronic devices for the development of novel light therapy concepts and powerful neuroscience research tools.

bioengineering↗