• Animals
• Bone Marrow
• Bone Neoplasms/secondary
• Bone and Bones
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Spine
• Tumor Microenvironment

• F32 CA254147 NCI NIH HHS
• I01 BX001370 BLRD VA
• R21 NS107879 NINDS NIH HHS
• R35 HL144481 NHLBI NIH HHS
• P01 CA093900 NCI NIH HHS
• R01 HL153028 NHLBI NIH HHS
• National Institutes of Health
• Rogel Cancer Center
• U.S. Department of Defense
• U.S. Department of Veterans Affairs
• Society of Neurological Surgeons

• Diagnosis
• Diffusion-weighted imaging
• Dynamic contrast–enhanced magnetic resonance imaging
• Follow-up
• Magnetic resonance imaging
• Monoclonal gammopathy of undetermined significance
• Multiple myeloma
• Smouldering myeloma
• Staging

• mesenchymal stem cells
• metabolic syndrome

• R21DE028265 U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)
• R01 DE017102 NIDCR NIH HHS
• S10 OD023457 NIH HHS
• R01DE017102 U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)
• R21 DE028265 NIDCR NIH HHS
• P30 CA054174 NCI NIH HHS
• UL1 TR001120 NCATS NIH HHS
• U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR)

Aging is an inescapable complex physiological but extendable process, and all cells, including stem cells, are altered over time. Diverse mechanism(s) could modulate stem cell number, their proliferation rate, and promote tissue repair during aging that leads to longevity. However, the factors that could restore aging stem cell potency and would lead to healthy aging are not fully identified. Here we show that maintaining cytosolic Ca²⁺ levels was essential for modulating stem cells function in aged mesenchymal stem cells (MSCs). Increasing external Ca²⁺ induced spindle shape stem cell morphology and maintained stem cell surface marker expression in aged bone marrow-derived MSCs. Similarly, stem cell survival and proliferation of aged MSCs was dependent on cytosolic Ca²⁺ levels. Importantly, Ca²⁺ entry potentiated cell cycle progression, and stem cell potential was increased in cells incubated with higher external Ca²⁺. Moreover, blocking Ca²⁺ entry using SKF 96365, decreased stem cell survival and its proliferation but, treatment with 2-APB did not significantly affected cell proliferation, rather only modulated cell viability. Evaluation of Ca²⁺ entry channels, showed that TRPC1/Orai1/Orai3 and their regulator STIM1 was essential for MSCs proliferation/viability as gene silencing of Orai1/Orai3/TRPC1/STIM1 significantly inhibited stem cell viability. Finally, MSCs isolated from aged mice that were subjected to higher Ca²⁺ levels, were able to rescue age-induced loss of MSCs function. Together these results suggest that Ca²⁺ entry is essential for preventing the loss of aged stem cell function and supplementing Ca²⁺ not only restored their proliferative potential but, allowed them to develop into younger stem cell lineages that could be critical for regenerative medicine.

• Aged stem cells and potency
• Calcium channels
• Cell proliferation/cell cycle
• Cell viability
• Stem cell function

The bone marrow (BM) is key to protective immunological memory because it harbors a major fraction of the body’s plasma cells, memory CD4+ and memory CD8+ T-cells. Despite its paramount significance for the human immune system, many aspects of how the BM enables decade-long immunity against pathogens are still poorly understood. In this review, we discuss the relationship between BM survival niches and long-lasting humoral immunity, how intrinsic and extrinsic factors define memory cell longevity and show that the BM is also capable of adopting many responsibilities of a secondary lymphoid organ. Additionally, with more and more data on the differentiation and maintenance of memory T-cells and plasma cells upon vaccination in humans being reported, we discuss what factors determine the establishment of long-lasting immunological memory in the BM and what we can learn for vaccination technologies and antigen design. Finally, using these insights, we touch on how this holistic understanding of the BM is necessary for the development of modern and efficient vaccines against the pandemic SARS-CoV-2.

• B-cells
• COVID-19
• SARS-CoV-2
• T-cells
• bone marrow
• infection
• memory
• plasma cells
• residency
• vaccination

Stem cells hold indefinite self-renewable capability that can be differentiated into all desired cell types. Based on their plasticity potential, they are divided into totipotent (morula stage cells), pluripotent (embryonic stem cells), multipotent (hematopoietic stem cells, multipotent adult progenitor stem cells, and mesenchymal stem cells [MSCs]), and unipotent (progenitor cells that differentiate into a single lineage) cells. Though bone marrow is the primary source of multipotent stem cells in adults, other tissues such as adipose tissues, placenta, amniotic fluid, umbilical cord blood, periodontal ligament, and dental pulp also harbor stem cells that can be used for regenerative therapy. In addition, induced pluripotent stem cells also exhibit fundamental properties of self-renewal and differentiation into specialized cells, and thus could be another source for regenerative medicine. Several diseases including neurodegenerative diseases, cardiovascular diseases, autoimmune diseases, virus infection (also coronavirus disease 2019) have limited success with conventional medicine, and stem cell transplantation is assumed to be the best therapy to treat these disorders. Importantly, MSCs, are by far the best for regenerative medicine due to their limited immune modulation and adequate tissue repair. Moreover, MSCs have the potential to migrate towards the damaged area, which is regulated by various factors and signaling processes. Recent studies have shown that extracellular calcium (Ca²⁺) promotes the proliferation of MSCs, and thus can assist in transplantation therapy. Ca²⁺ signaling is a highly adaptable intracellular signal that contains several components such as cell-surface receptors, Ca²⁺ channels/pumps/exchangers, Ca²⁺ buffers, and Ca²⁺ sensors, which together are essential for the appropriate functioning of stem cells and thus modulate their proliferative and regenerative capacity, which will be discussed in this review.

• Ca²⁺ signaling
• Ca²⁺ channels
• Transient receptor potential channel 1/Orai1 stem cells
• Regenerative medicine
• Stem cells

• MRI
• edema
• ganglion
• healthy
• joint fluid
• normal
• pediatric
• wrist

• Ankle maturation 1
• Calcaneal apophysis 2

• Bone marrow
• Columna vertebral
• Diffusion
• Difusión
• Magnetic resonance
• Metastases
• Metástasis
• Médula ósea
• Resonancia magnética
• Spinal column

For now, magnetic resonance (MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast and non-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1W, fat-suppressed T2W and short tau inversion recovery (STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrasted-enhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject’s health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up.

• Magnetic resonance imaging
• Normal
• Spinal
• Marrow
• Variants