MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration.

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds. Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data. Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection. Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.

Molecular crosstalk between insulin-like growth factors and follicle-stimulating hormone in the regulation of granulosa cell function.

Background: The last phase of folliculogenesis is driven by follicle-stimulating hormone (FSH) and locally produced insulin-like growth factors (IGFs), both essential for forming preovulatory follicles. Methods: This review discusses the molecular crosstalk of the FSH and IGF signaling pathways in regulating follicular granulosa cells (GCs) during the antral-to-preovulatory phase. Main findings: IGFs were considered co-gonadotropins since they amplify FSH actions in GCs. However, this view is not compatible with data showing that FSH requires IGFs to stimulate GCs, that FSH renders GCs sensitive to IGFs, and that FSH signaling interacts with factors downstream of AKT to stimulate GCs. New evidence suggests that FSH and IGF signaling pathways intersect at several levels to regulate gene expression and GC function. Conclusion: FSH and locally produced IGFs form a positive feedback loop essential for preovulatory follicle formation in all species. Understanding the mechanisms by which FSH and IGFs interact to control GC function will help design new interventions to optimize follicle maturation, perfect treatment of ovulatory defects, improve in vitro fertilization, and develop new contraceptive approaches.

Biomarkers in retinopathy of prematurity: a systematic review and meta-analysis.

Aim: Retinopathy of prematurity is a significant global cause of childhood blindness. This study aims to identify serum biomarkers that are associated with the development of ROP. Methods: A systematic review and meta-analysis was conducted using PRISMA guidelines. Three databases were searched (Pubmed, Scopus and Web of Science) from 2003 to March 2023. Only studies investigating serum biomarker levels in preterm infants (<37 weeks gestation) were included. Results: Meta-analysis suggests that low serum IGF-1 levels have a strong association with the development of ROP [SMD (95% CI) of -.46 [-.63, -.30], p < .001]. Meta-analysis suggests that higher serum glucose levels were associated with the development of ROP [SMD (95% CI) of 1.25 [.94, 1.55], p < .001]. Meta-analysis suggests that thrombocytopenia is associated with the development of ROP [SMD (95% CI) of -.62 [-.86, -.37], p < .001]. Conclusion: Low levels of serum IGF-1, high levels of serum glucose and thrombocytopenia all appear to have the strongest association with the development of ROP out of the 63 biomarkers investigated in this review. These associations highlight their potential use as diagnostic biomarkers in ROP, though further research is needed to establish the exact relationship between these biomarkers and disease pathogenesis.

Growth Factors and Microneedling in Alopecia Areata: A Narrative Review.

Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss on the scalp or other hair-bearing surfaces. Various signalling molecules regulate the hair cycle and hair follicle regeneration. These include genes, growth factors, nuclear receptors, cytokines, and subcellular signalling pathways. Growth factors can cause the vascular endothelium and dermal fibroblasts to proliferate, extend the anagen phase, and delay the initiation of catagen in the hair follicle, thereby promoting hair growth. Microneedling causes the release of growth factors and has been shown to help high-molecular-weight drugs penetrate the stratum corneum and hair follicles. These recent discoveries regarding the pathogenesis of AA have resulted in the development of promising therapies. Herein, this article reviews the use of growth factors and microneedling in the treatment of AA and explores their efficacy and safety. Treatment with growth factors and microneedling appears to be highly effective for AA, with no major adverse effects, and may provide a new option for hair regeneration therapy. To support the efficacy of growth factors and microneedling for AA treatment, additional large-scale studies of patients with AA are needed.

Evaluation of a Quality Improvement Process for Health-System Retention of Long Acting Growth Factors Prescriptions in the Pediatric Oncology Population.

OBJECTIVE: Granulocyte-colony stimulating factor (GCSF) products are often used in pediatric patients with malignant diagnoses to reduce the time that the patient is neutropenic. Long-acting GCSF products have been shown to be non-inferior to daily dosing of GCSF products, and are becoming more desired by patients and families. Insurance companies often require a prior authorization prior to approving the use of the long-acting GCSF products. This process has proven challenging leading to treatment delays and missed doses. The purpose of this study is to evaluate a quality improvement process for the prescribing and dispensing of long-acting GCSF to better serve pediatric patients within a single health care system. METHODS: This is a single-center, retrospective chart review with the purpose of collecting data to compare prescription retention before and after the improvement intervention. Study timeline includes all doses of long-acting GCSF prescribed for pediatric oncology patients between June 2020-June 2021 compared with July 2021-March 2022. On June 30, 2021, educational information was provided to the appropriate stakeholders regarding the change in practice. RESULTS: A total of 31 patients were included in the review, with 22 patients prior to the intervention (115 prescriptions), and 9 patients after the intervention (43 prescriptions). There was a 37.8% increase in health system prescription retention (15.7% vs 53.5%). CONCLUSIONS: Pharmacist directed long-acting GCSF prescription destination and a dedicated prior-authorization team led to an increase in prescription retention for patients regardless of payer mandated outpatient pharmacy.

How to explain the beneficial effects of platelet-rich plasma.

Platelet-rich plasma (PRP) is the platelet and leukocyte-containing plasmatic fraction of anticoagulated autologous blood. While evidence supporting the clinical use of PRP in dentistry is low, PRP is widely used in sports medicine, orthopedics, and dermatology. Its beneficial activity is commonly attributed to the growth factors released from platelets accumulating in PRP; however, evidence is indirect and not comprehensive. There is thus a demand to revisit PRP with respect to basic and translational science. This review is to (i) recapitulate protocols and tools to prepare PRP; (ii) to discuss the cellular and molecular composition of PRP with a focus on platelets, leukocytes, and the fibrin-rich extracellular matrix of coagulated plasma; and finally (iii) to discuss potential beneficial effects of PRP on a cellular and molecular level with an outlook on its current use in dentistry and other medical fields.

Comparison of the Clinical Effectiveness of Intra-Articular Injection with Different Substances After TMJ Arthroscopy: A Systematic Review and Meta-Analysis.

Objective: This systematic review aims to describe the clinical outcomes after TMJ arthroscopy followed by intra articular infiltration with different substances. Materials and Methods: A literature search was carried out, the variables were Arthroscopy with different substances, pain and maximal mouth opening. The inclusion criteria were articles that reported infiltration of different substances after arthroscopy. Case series, observational studies, and randomized clinical trials were included. Exclusion criteria were studies that included arthrocentesis, animal studies, connective tissue disease, patients with previous surgeries. Results: Of the 5 studies finally included, the population studied were 346 subjects, of which 315 were female. The mean age was 34.7 (16-77). Regarding diagnoses, Wilkes III and Wilkes IV were taken into account. The most commonly used substance was sodium hyaluronate/hyaluronic acid in 4 of the 5 studies. Conclusion: Multiple substances have been infiltrated within the temporomandibular joint, with sodium hyaluronate/hyaluronic acid being the most studied. However, the benefit of substances like ATM artroscopia adyuvantes has not been clearly established. It is recommended in future studies that the substances and results be evaluated in the same way to obtain more homogeneous studies.

Interactions of proteins with heparan sulfate.

Heparan sulfate (HS) is a glycosaminoglycan, polysaccharides that are considered to have arisen in the last common unicellular ancestor of multicellular animals. In this light, the large interactome of HS and its myriad functions in relation to the regulation of cell communication are not surprising. The binding of proteins to HS determines their localisation and diffusion, essential for embryonic development and homeostasis. Following the biosynthesis of the initial heparosan polymer, the subsequent modifications comprise an established canonical pathway and a minor pathway. The more frequent former starts with N-deacetylation and N-sulfation of GlcNAc residues, the latter with C-5 epimerisation of a GlcA residue adjacent to a GlcNAc. The binding of proteins to HS is driven by ionic interactions. The multivalent effect arising from the many individual ionic bonds between a single protein and a polysaccharide chain results in a far stronger interaction than would be expected from an ion-exchange process. In many instances, upon binding, both parties undergo substantial conformational change, the resulting hydrogen and van der Waal bonds contributing significant free energy to the binding reaction. Nevertheless, ionic bonds dominate the protein-polysaccharide interaction kinetically. Together with the multivalent effect, this provides an explanation for the observed trapping of HS-binding proteins in extracellular matrix. Importantly, individual ionic bonds have been observed to be dynamic; breaking and reforming, while the protein remains bound to the polysaccharide. These considerations lead to a model for 1D diffusion of proteins in extracellular matrix on HS, involving mechanisms such as sliding, chain switching and rolling.

A Novel Fibrin Matrix Derived from Platelet-Rich Plasma: Protocol and Characterization.

Although fibrin matrices derived from Platelet-Rich Plasma (PRP) are widely used in regenerative medicine, they have some limitations that can hinder their application. Modifying the composition of the PRP-derived fibrin matrix may improve its properties, making it suitable for certain medical uses. Three types of fibrin matrices were obtained: a PRP-derived fibrin matrix (FM), a PRP-derived fibrin matrix with a high fibrinogen content and platelets (FM-HFP) and a PRP-derived fibrin matrix with a high fibrinogen content (FM-HF). The fibrinogen levels, biomechanical properties and cell behavior were analyzed. The presence of platelets in the FM-HFP generated an inconsistent fibrin matrix that was discarded for the rest of the analysis. The fibrinogen levels in the FM-FH were higher than those in the FM (p < 0.0001), with a concentration factor of 6.86 ± 1.81. The values of clotting and swelling achieved using the FM-HF were higher (p < 0.0001), with less clot shrinkage (p < 0.0001). The FM had a significantly higher stiffness and turned out to be the most adherent composition (p = 0.027). In terms of cell viability, the FM-HF showed less cell proliferation but higher live/dead ratio values (p < 0.01). The increased fibrinogen and platelet removal in the FM-HF improved its adhesion and other biomechanical properties without affecting cell viability.

Emerging therapies targeting growth factors in hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a primary liver cancer that commonly arises in the background of chronic liver inflammation and/or cirrhosis. Chronic liver inflammation results in the production of different growth factors, remodeling of the microenvironment architecture into fibrosis, and eventually carcinogenesis. Overexpression of some growth factors has been associated with worse prognosis in patients with HCC. Targeted therapies against growth factors may disrupt cell signaling and the mechanisms that allow for cell survival (e.g. angiogenesis, proliferation, metastases). AREAS COVERED: We herein review potential growth factor targets of HCC and the limited research that exists regarding targeted therapy of these ligands and their receptors. We performed an extensive literature search to investigate preclinical studies, clinical research, and clinical trials. EXPERT OPINION: Systemic therapy for patients with HCC is continuing to evolve. Anti-angiogenic therapy holds the most promise among targeted therapy for growth factors among patients with HCC. Improving our understanding of growth factors in HCC will hopefully lead to the development of new targeted therapies and strategies for combination therapies with immune checkpoint inhibitors.

Elucidating the mechanism of corneal epithelial cell repair: unraveling the impact of growth factors.

The repair mechanism for corneal epithelial cell injuries encompasses migration, proliferation, and differentiation of corneal epithelial cells, and extracellular matrix remodeling of the stromal structural integrity. Furthermore, it involves the consequential impact of corneal limbal stem cells (LSCs). In recent years, as our comprehension of the mediating mechanisms underlying corneal epithelial injury repair has advanced, it has become increasingly apparent that growth factors play a pivotal role in this intricate process. These growth factors actively contribute to the restoration of corneal epithelial injuries by orchestrating responses and facilitating specific interactions at targeted sites. This article systematically summarizes the role of growth factors in corneal epithelial cell injury repair by searching relevant literature in recent years, and explores the limitations of current literature search, providing a certain scientific basis for subsequent basic research and clinical applications.

Improving the mechanical and biological functions of cell sheet constructs: The interplay of human-derived periodontal ligament stem cells, endothelial cells and plasma rich in growth factors.

OBJECTIVE: The aim of this study was to produce and characterize triple-layered cell sheet constructs with varying cell compositions combined or not with the fibrin membrane scaffold obtained by the technology of Plasma Rich in Growth Factors (mPRGF). MATERIALS AND METHODS: Human primary cultures of periodontal ligament stem cells (hPDLSCs) were isolated, and their stemness nature was evaluated. Three types of triple-layered composite constructs were generated, composed solely of hPDLSCs or combined with human umbilical vein endothelial cells (HUVECs), either as a sandwiched endothelial layer or as coculture sheets of both cell phenotypes. These three triple-layered constructs were also manufactured using mPRGF as cell sheets' support. Necrosis, glucose consumption, secretion of extracellular matrix proteins and synthesis of proangiogenic factors were determined. Histological evaluations and proteomic analyses were also performed. RESULTS: The inclusion of HUVECs did not clearly improve the properties of the multilayered constructs and yet hindered their optimal conformation. The presence of mPRGF prevented the shrinkage of cell sheets, stimulated the metabolic activity and increased the matrix synthesis. At the proteome level, mPRGF conferred a dramatic advantage to the hPDLSC constructs in their ability to provide a suitable environment for tissue regeneration by inducing the expression of proteins necessary for bone morphogenesis and cellular proliferation. CONCLUSIONS: hPDLSCs' triple-layer construct onto mPRGF emerges as the optimal structure for its use in regenerative therapeutics. CLINICAL RELEVANCE: These results suggest the suitability of mPRGF as a promising tool to support cell sheet formation by improving their handling and biological functions.

Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization.

BACKGROUND: Cytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors. METHODS: Bidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty-one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome-wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate-to-vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10 min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta-GWAS and the UK Biobank, and sample sizes ranged from 69 537 to 472 174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut-off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5 × 10-6 and 5 × 10-8). Inverse-variance weighted, MR-Egger and weighted median were employed to estimate the causality. RESULTS: Twenty-seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin-16), CTACK (cutaneous T-cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet-derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956-0.998] for EWGSOP and 0.933 [0.874-0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995-1.000]) and AWCU10 (1.008 [1.003-1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007-1.019] for EWGSOP and 1.090 [1.041-1.142] for FNIH), AWCU10 (0.990 [0.986-0.994]) and telomere length (0.998 [0.983-0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001-1.063] for EWGSOP), AWCU10 (0.994 [0.988-1.000] and 0.993 [0.988-0.998]) and telomere length (1.006 [1.000-1.012]). PDGFbb may causally relate to AALM (1.016 [1.001-1.030]) and telomere length (1.011 [1.007-1.015]). Reserve MR analyses also proved their unidirectional causal effects. CONCLUSIONS: Twenty-seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

Adipocyte PI3K links adipostasis with baseline insulin secretion at fasting through an adipoincretin effect.

Insulin-PI3K signaling controls insulin secretion. Understanding this feedback mechanism is crucial for comprehending how insulin functions. However, the role of adipocyte insulin-PI3K signaling in controlling insulin secretion in vivo remains unclear. Using adipocyte-specific PI3Kα knockout mice (PI3KαAdQ) and a panel of isoform-selective PI3K inhibitors, we show that PI3Kα and PI3Kß activities are functionally redundant in adipocyte insulin signaling. PI3Kß-selective inhibitors have no effect on adipocyte AKT phosphorylation in control mice but blunt it in adipocytes of PI3KαAdQ mice, demonstrating adipocyte-selective pharmacological PI3K inhibition in the latter. Acute adipocyte-selective PI3K inhibition increases serum free fatty acid (FFA) and potently induces insulin secretion. We name this phenomenon the adipoincretin effect. The adipoincretin effect operates in fasted mice with increasing FFA and decreasing glycemia, indicating that it is not primarily a control system for blood glucose. This feedback control system defines the rates of adipose tissue lipolysis and chiefly controls basal insulin secretion during fasting.

What Kind of Dressing Is Important to Ensure Wound Healing With the Application of Platelet-Rich Plasma in Chronic Ulcers?

Wound healing is an intricate process of tissue regeneration that depends on the simultaneous presence of immunological and microenvironmental factors. The significant role of platelets and their granules in the wound-healing process has led to extensive research on their potential as a therapeutic intervention in different areas, including chronic wounds and aesthetic therapies. Saltwater aids in purification and promotes healing by utilizing osmosis. Sodium chloride, the chemical component present in salt, induces the extrusion of fluids from cells upon contact. If the liquids in issue are bacterial, they will also be ejected, assisting in the cleansing of the skin. Desiccation, often known as the drying out of injured cells, is well-known for its antibacterial properties and subsequent ability to reduce inflammation. This case series aims to investigate the advantages of using saltwater dressing following platelet-rich plasma therapy for chronic wounds.

Blood-Derived Eye Drops for the Treatment of Corneal Neuropathic Pain.

Blood-derived preparations, including autologous or allogenic serum, umbilical cord serum/plasma, and platelet-rich plasma eye drops, contain various growth factors, cytokines, and immunoglobulins that resemble natural tears. These components play important roles in corneal cell migration, proliferation, and wound healing. Blood-derived eye drops have demonstrated clinical effectiveness across a spectrum of ocular surface conditions, encompassing dry eye disease, Sjögren's syndrome, graft-versus-host disease, and neuropathic corneal pain (NCP). Currently, management of NCP remains challenging. The emergence of blood-derived eye drops represents a promising therapeutic approach. In this review, we discuss the benefits and limitations of different blood-derived eye drops, their mechanisms of action, and treatment efficacy in patients with NCP. Several studies have demonstrated the clinical efficacy of autologous serum eye drops in relieving pain and pain-like symptoms, such as allodynia and photoallodynia. Corneal nerve parameters were also significantly improved, as evidenced by increased nerve fiber density, length, nerve reflectivity, and tortuosity, as well as a decreased occurrence of beading and neuromas after the treatment. The extent of nerve regeneration correlated with improvement in patient-reported photoallodynia. Cord plasma eye drops also show potential for symptom alleviation and corneal nerve regeneration. Future directions for clinical practice and research involve standardizing preparation protocols, establishing treatment guidelines, elucidating underlying mechanisms, conducting long-term clinical trials, and implementing cost-effective measures such as scaling up manufacturing. With ongoing advancements, blood-derived eye drops hold promise as a valuable therapeutic option for patients suffering from NCP.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

PURPOSE: To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. METHODS: Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 h) or delayed administration (after 72 h) of HiDAC. RESULTS: The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16 months versus 19 months, p = 0.69) and overall survival (21 months versus 31 months, p = 0.47). CONCLUSION: A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

Roles of fibroblast growth factors in the treatment of diabetes.

Diabetes affects about 422 million people worldwide, causing 1.5 million deaths each year. However, the incidence of diabetes is increasing, including several types of diabetes. Type 1 diabetes (5%-10% of diabetic cases) and type 2 diabetes (90%-95% of diabetic cases) are the main types of diabetes in the clinic. Accumulating evidence shows that the fibroblast growth factor (FGF) family plays important roles in many metabolic disorders, including type 1 and type 2 diabetes. FGF consists of 23 family members (FGF-1-23) in humans. Here, we review current findings of FGFs in the treatment of diabetes and management of diabetic complications. Some FGFs (e.g., FGF-15, FGF-19, and FGF-21) have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes, and their therapeutic roles in diabetes are currently under investigation in clinical trials. Overall, the roles of FGFs in diabetes and diabetic complications are involved in numerous processes. First, FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production. Second, modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components, promote diabetic wound healing process and bone repair, and inhibit cancer cell proliferation and migration. Finally, FGFs can regulate the activation of glucose-excited neurons and the expression of thermogenic genes.

Pain is what hurts: An exploration of perception and management of pain in peripheral blood stem cell donors.

BACKGROUND: Pain is a side effect of Granulocyte-Colony Stimulating Factor (G-CSF) administration. This prospective study investigates various aspects including pain perception occurring in Peripheral Blood Stem Cell (PBSC) donors. MATERIALS AND METHODS: Related and unrelated PBSC donors were prospectively studied. Donors recorded pain symptoms during the four-day period of G-CSF administration using the McGill Pain Questionnaire, a Visual Analog Scale and a pain diary. RESULTS: There were 208 donors included, 102 (49%) related and 106 (51%) unrelated donors. Ninety-two percent of all reported the occurrence of pain. Moderate or severe pain was reported by 52%. No differences were found between related and unrelated donors. Pain occurred more often in females (p = 0.035). Relatively young donors (age 16-30 years) more frequently showed to have pain in comparison to older donors (>50 years) (p = 0.006). Musculoskeletal pain was most frequently distributed in the gluteal and lower back region (65-71%). Irrespective of the pain location, pain was most often described as nagging, annoying, however tolerable. Donors experiencing pain most on days of G-CSF administration, most frequently occurring during relaxation or at night. Sleep-mode was often affected. The use of paracetamol (acetaminophen) was sufficient for all but one donor. CONCLUSION: This is the first study to describe different aspects of pain associated with G-CSF administration in donors. Although the observed pain was tolerable, it should never be neglected. Knowledge derived from this study is of use for staff members involved in donor information and care management.