Impact of Nutritional Status on Antibody Titer After Booster mRNA COVID-19 Vaccine Among Elderly Adults in Japan.

BACKGROUND: Published studies on mRNA coronavirus disease 2019 (COVID-19) vaccine effects focus on younger individuals, comprising the majority of the workforce. Studies in elderly adults are sparse. METHODS: In total, 107 subjects were recruited (median age 78; interquartile range [IQR], 58.5-90.5; range, 35-105 years). Factors associated with antibody titer after the third mRNA COVID-19 vaccination were compared between 49 elderly (age ≥80; median, 94; IQR, 86-97; range, 80-105 years) and 58 younger (age ≤79; median, 61; IQR, 46-71; range, 35-79 years) adults. RESULTS: Among body mass index (BMI) categories, the group of underweight elderly adults had a lower antibody titer compared to those with normal weight (P < .01 after 1, 3, and 5 months). Elderly adults were less likely to maintain effective antibody titer (≥4160 AU/mL) compared to younger adults: 76% versus 98%, P < .001 after 1 month, and 45% versus 78%, P < .001 after 3 months. Elderly adults who maintained effective antibody titer for 5 months had a higher BMI (22.9 kg/m2 vs 20.1 kg/m2, P = .02), and were less likely to have underweight BMI (0% vs 31%, P = .02) compared to the subjects who failed to maintain effective antibody titer. CONCLUSIONS: These results highlight the impact of nutritional status and the deleterious effect of underweight BMI on antibody titer and its maintenance among elderly adults following booster mRNA COVID-19 vaccination.

[Creutzfeldt-Jakob Disease and Lyodura:A Special Reference to Prion Disease Control in the Field of Neurosurgery].

In Japan, 156 cases of dura mater-transplanted Creutzfeldt-Jakob disease(dCJD)with a history of Lyodura transplantation have been confirmed until February 2022, with only a few new cases still being identified. The history of Lyodura transplantation is one involving a neurosurgical procedure. The cumulative global number of cases of bovine spongiform encephalopathy-related variant CJD(BSE-related vCJD), which has shaken societies around the world, is 232 as of 2019. Thus, the impact of dCJD on the society in Japan needs no explanation. Thanks to the world's concerted efforts in research and countermeasures, medically induced prion diseases are finally becoming a thing of the past. However, due to the extremely long incubation period of CJD and the difficulty of tracing the source of infection, immediate action in the event of an outbreak is not possible, and efforts must focus on preventing disease outbreaks. Independent of this, approximately 200 cases of solitary and hereditary prion diseases occur annually in Japan. If neurosurgery must be performed on such patients, secondary transmission of prion disease by neurosurgical instruments must be prevented. Therefore, sterilization methods for neurosurgical instruments are critical, and various measures including sterilization methods have been determined and published by a research group designated by the Japanese Ministry of Health, Labour and Welfare. The sterilization of neurosurgical instruments should comply with the latest guidelines that are published by this study group.

Gastric cancer deaths by age group in Japan: Outlook on preventive measures for elderly adults.

In February 2013, Japan became the first country in the world to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system. Now that eradication therapy is covered by NHI, its usage has increased dramatically, and gastric cancer deaths have begun to decrease. We undertook a detailed epidemiological analysis to investigate effects of expanded NHI coverage for H. pylori eradication therapy on gastric cancer deaths in specific age groups. Numbers of gastric cancer deaths were determined by referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan - 2018" published by the Foundation for Promotion of Cancer Research. Gastric cancer deaths across all age groups have been clearly decreasing since 2013, but deaths of people aged 80 years and older are still increasing. The number of gastric cancer deaths in people aged in their 80s was 2 times higher than in people aged in their 70s and 4 times higher than in people aged in their 60s. The number of people in their 80s who had an endoscopy was less than half that of people in their 60s and 70s. The eradication therapy has increased dramatically, and gastric cancer deaths are clearly decreasing in Japan. However, this decrease in deaths has not extended to elderly adults aged in their 80s, which suggests that measures to prevent gastric cancer in people aged 80 years and older will be critical to achieving the mission of eliminating gastric cancer in Japan.

P. gingivalis Lipopolysaccharide Stimulates the Upregulated Expression of the Pancreatic Cancer-Related Genes Regenerating Islet-Derived 3 A/G in Mouse Pancreas.

Although epidemiological studies have shown a relationship between periodontal disease and pancreatic cancer, the molecular mechanisms involved remain unclear. In this study, the effects of systemic administration of Porphyromonas gingivalis lipopolysaccharide (PG-LPS) on gene expression were comprehensively explored in mouse pancreas that did not demonstrate any signs of inflammation. PG-LPS was prepared in physiological saline and intraperitoneally administered to male mice at a concentration of 5 mg/kg every 3 days for 1 month. After extracting total RNA from the excised mice pancreas, a comprehensive DNA microarray analysis of gene expression was performed. Tissue specimens were also subjected to hematoxylin-eosin staining and immunohistochemistry using anti-regenerating islet-derived 3A and G (Reg3A/G) antibody. ImageJ software was used to quantify the area of Reg3A/G positive cells in pancreatic islets by binarizing image date followed by area extraction. The results were compared using Mann-Whitney U test. Data are presented as mean ± standard deviation (SD) with p < 0.05 considered as significant. Reg3G, a gene related to pancreatic cancer, was one of the 10 genes with the highest levels of expression in the pancreas stimulated with PG-LPS. The comprehensive analysis revealed a 73-fold increase in Reg3G expression level in the PG-LPS group when compared with the control group; in addition, the expression level of Reg3A was increased by 11-fold in the PG-LPS group. Image analysis showed that the ratio of Reg3A/G positive cells was higher in the PG-LPS group than the control. Immunostaining showed the presence of Reg3A/G-positive cells in the alpha-cell equivalent areas around the islets of Langerhans in the PG-LPS group. These results support the notion that periodontal disease may be a risk factor for pancreatic cancer.

Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan.

BACKGROUND: In Japan, there have been approximately 50 000 deaths from gastric cancer annually for over 40 years with little variation. It has been reported that most gastric cancers in Japan are caused by Helicobacter pylori infection. H. pylori eradication therapy was approved for patients with chronic gastritis by the Japanese national health insurance scheme in February 2013 for patients with an endoscopic diagnosis of chronic gastritis is positive for H. pylori. We examined the effect on gastric cancer death rate 4 years after expansion of health insurance coverage. AIM: We conducted an epidemiological study and analyzed trends in prescription for H. pylori eradication therapy. We used the electronic medical claims database from Hokkaido, Japan to evaluate the impact of expansion of national health insurance coverage for H. pylori eradication therapy on deaths from gastric cancer. METHODS: Data on deaths from gastric cancer were obtained from the Japanese Ministry of Health, Labour and Welfare and the Cancer Statistics in Japan (2015). Analysis of electronic claims records was performed using the National Database, mainly focusing on Hokkaido. Prescriptions for H. pylori eradication therapy and the number of patients treated for gastric cancer were also extracted from the Hokkaido database. RESULTS: Approximately 1.5 million prescriptions for H. pylori eradication therapy were written annually. Gastric cancer deaths fell each year: 48 427 in 2013, 47 903 in 2014, 46 659 in 2015, and 45 509 in 2016, showing a significant decrease after expansion of insurance coverage for H. pylori eradication therapy (P<.0001). CONCLUSIONS: Prescriptions for H. pylori eradication therapy increased markedly after approval of the gastritis indication by the national health insurance scheme and was associated with a significant decrease in gastric cancer deaths.

Re-survey of 16 Japanese patients with advanced-stage hereditary motor sensory neuropathy with proximal dominant involvement (HMSN-P): Painful muscle cramps for early diagnosis.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an intractable neurological disease with autosomal dominant inheritance, four-limb weakness, sensory impairment, and a slowly progressive course. HMSN-P patients develop four-limb paralysis at the advanced-stage, as in amyotrophic lateral sclerosis (ALS). There is a natural 20- to 30-year course from initial painful muscle cramps and four-limb paralysis to respiratory dysfunction. A delay in the diagnosis of HMSN-P occurs due to the 20- to 30-year span from the initial symptom(s) to typical quadriplegia. Its early diagnosis is important, but the involvement of painful muscle cramps as an early symptom has not been clear. Following our earlier survey, we conducted a re-survey focusing on painful muscle cramps, assistive-device use, and hope for specific therapies in 16 Japanese patients with advanced-stage HMSN-P. Fifteen patients presented painful muscle cramps as the initial symptom, and muscle cramps in the lower abdomen including the flank were described by 10 of the patients. The presence of painful muscle cramps including those in the abdominal region may be a clue for the early diagnosis of HMSN-P. Painful abdominal cramps have not described in related diseases, e.g., ALS, spinal muscular atrophy, and Charcot-Marie-Tooth disease. Recent patient-welfare improvements and advances in assistive devices including robot-suit assistive limbs are delaying the terminal state of HMSN-P. Regarding specific therapies for HMSN-P, many patients choose both nucleic acid medicine and the application of induced pluripotent stem cells as a specific therapy for HMSN-P.

Nine Cases of SARS-CoV-2-PCR-positive Samples Showed No Increase of Antibodies Against SARS-CoV-2.

BACKGROUND/AIM: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been affecting Hokkaido, Japan since late February 2020 until present. The aim of this study was to report the relationship between anti-SARS-CoV-2 antibody-positive and SARS-CoV-2 PCR-positive cases by analyzing anti-SARS-CoV-2 antibodies (IgG and total-Ig). PATIENTS AND METHODS: Serum samples were collected from care workers and nurses in two nursing homes and two hospitals which underwent virus outbreak. All people were confirmed to be SARS-CoV-2-positive by RT-qPCR and their sera was analyzed for anti-SARS-CoV-2 antibodies (IgG and total-Ig). RESULTS: Although 34 out of 43 samples (79.1%) showed enough amount of anti-SARS-CoV-2 antibodies, 9 RT-qPCR -positive samples (20.9%) showed absence of anti-SARS-CoV-2 antibodies in their sera. CONCLUSION: The results that 20.9% of RT-qPCR-positive samples with SARS-CoV-2 showed absence of anti-SARS-CoV-2 antibodies provides a possibility that the innate immune reaction could eliminate the virus without activating adaptive immune reaction.

Basic fibroblast growth factor is beneficial for postoperative color uniformity in split-thickness skin grafting.

Color changes of visible and exposed body surfaces, such as the face and extremities, after burn injury or surgery, such as skin grafting, flap, or sclerotherapy for vascular malformations, are sometimes a concern. The consequences reduce the satisfaction of both patients and physicians. An easy and reproducible method has not yet been established for an objective analysis of color changes; therefore, we tested a hand-held color analyzer (NF-333; Nippon Denshoku Co. Ltd) with data transport to a computer database and analysis software for posttreatment skin color change. The parameters included L, a, and b, which measure clarity, red, and yellow, respectively. Two groups were prospectively divided with 20 (11 females and nine males) patients per group. One group received skin grafting plus basic fibroblast growth factor (bFGF) spray daily and the other group received only skin grafting. The patients were randomized by the date of their first visit to our hospital. Patients were treated with bFGF on odd days, while patients who came on even days were included in the non-bFGF-treated group. The donor site for skin grafting was the lateral thighs and the thickness was similar in both groups. The results were compared at 1-year posttreatment follow-up. Clinical and objective assessments of the scars were performed 1 to years after complete healing. Color change differentials in comparison with the surrounding skin were lower with bFGF treatment in all parameters (p<0.01), along with clinical assessment with the Vancouver Scar Scale; therefore, the treatment contribute to a better color match with skin grafting postoperatively.

Acceleration of sensory neural regeneration and wound healing with human mesenchymal stem cells in immunodeficient rats.

The sensory nerve is highly involved in lower extremity wound healing. In diabetic and vascular diseases, impaired nerve function and blood flow delay wound healing. Tissue regeneration using adult stem cells is a targeted therapeutic modality in disorders of nerve and blood supply. Effective delivery using an autologous vascularized fascial flap as a vehicle of stem cells leads to severed sensory nerve recovery, local tissue blood flow, and wound healing. Human MSCs (hMSCs) were transfected with green fluorescent protein (GFP) cDNA and tested for efficiency and proliferation in vitro. The nude rat model with femoral vessel and saphenous nerve severance and ligation was wrapped with a vascularized epigastric flap for GFP-hMSC, fibroblast growth factor-2 (FGF-2), or a combination of both after 2 weeks. Maximum nerve conduction velocity recovered to 70% of the presurgical level in the GFP-hMSC- and FGF-2-treated group at 2 weeks. Blood flow and nerve conduction velocity were positively correlated at 1 week. Wound healing in the ipsilateral paw had significantly improved by 1 week. Histologically, blood vessels and nerves are very organized, and regenerated neuron immunoreactivity of GAP-43 and a nerve regrowth marker of S-100 were remarkable in the human GFP (hGFP)-hMSC and FGF-2-treated group at 2 weeks; therefore, sensory nerve regeneration, blood flow, and wound healing were improved by the administration of stem cells and FGF-2 via a vascularized flap. This may be implicated in clinical denervated and reduced circulation tissue wound healing.

Basic fibroblast growth factor accelerates and improves second-degree burn wound healing.

Second-degree burns are sometimes a concern for shortening patient suffering time as well as the therapeutic choice. Thus, adult second-degree burn patients (average 57.8 +/- 13.9 years old), mainly with deep dermal burns, were included. Patients receiving topical basic fibroblast growth factor (bFGF) or no bFGF were compared for clinical scar extent, passive scar hardness and elasticity using a Cutometer, direct scar hardness using a durometer, and moisture analysis of the stratum corneum at 1 year after complete wound healing. There was significantly faster wound healing with bFGF, as early as 2.2 +/- 0.9 days from the burn injury, compared with non-bFGF use (12.0 +/- 2.2 vs. 15.0 +/- 2.7 days, p<0.01). Clinical evaluation of Vancouver scale scores showed significant differences between bFGF-treated and non-bFGF-treated scars (p<0.01). Both maximal scar extension and the ratio of scar retraction to maximal scar extension, elasticity, by Cutometer were significantly greater in bFGF-treated scars than non-bFGF-treated scars (0.23 +/- 0.10 vs. 0.14 +/- 0.06 mm, 0.59 +/- 0.20 vs. 0.49 +/- 0.15 mm: scar extension, scar elasticity, bFGF vs. non-bFGF, p<0.01). The durometer reading was significantly lower in bFGF-treated scars than in non-bFGF-treated scars (16.2 +/- 3.8 vs. 29.3 +/- 5.1, p<0.01). Transepidermal water loss, water content, and corneal thickness were significantly less in bFGF-treated than in non-bFGF-treated scars (p<0.01).

A basic fibroblast growth factor improves lower extremity wound healing with a porcine-derived skin substitute.

BACKGROUND: Although a number of cytokine or growth factor therapies for wound acceleration have been reported, few mentioned the quality of the outcome. The lower extremity is important in esthetics as well as in function, because it is exposed. Recently, a growth factor, namely basic growth factor (bFGF) is widely used for difficult wound healing with a porcine-derived bilayered artificial dermis for better wound closure. Thus, their combination use was tested clinically. METHODS: Sequential lower extremity reconstruction by an artificial dermis with or without bFGF administration and secondary split-thickness skin grafting was measured for hardness using a durometer, and the moisture parameters assessed such as effective contact coefficient, transepidermal water loss (TEWL), water content and thickness using a moisture meter for at least 6 months after the final procedure and compared with normal skin control. RESULTS: There was significantly less skin hardness using a durometer in bFGF treatment compared with non-bFGF treatment (16.2 +/- 3.83 vs. 29.2 +/- 4.94, p < 0.01). Effective contact coefficient, TEWL, water content, and thickness in non-bFGF treatment were all significantly greater than those in bFGF treatment, whereas water content and thickness in bFGF treatment were comparable with those of the control. CONCLUSION: The use of bFGF as artificial dermis for extensive and deeper tissue loss coverage demonstrated better reconstruction quality in terms of hardness using a durometer and the function of the stratum corneum by moisture analysis.

A polyurethane dressing is beneficial for split-thickness skin-graft donor wound healing.

Few comparative studies have been performed on the various wound-dressing materials or methods proposed for use. To clarify the efficacy of wound dressing, 35 patients (17 females, aged 44.8+/-26.86 years and 18 males, aged 35.4+/-29.70) were subjected to a prospective study comparing a polyurethane dressing and a hydrogel dressing for split-thickness skin donors from the lateral thighs. We examined their clinical usefulness such as accelerated healing time, frequency of changing the dressing, degree of pain, or amount of exudates, and performed moisture meter analysis at 1 month and 1 year after re-epithelialization, which reflects the quality of the stratum corneum and subsequent scarring. The polyurethane dressing was superior to hydrogel in the wound healing time, amount of exudates, and frequency of dressing changes: the hydrogel was better for regulating the degree of pain. There was a positive correlation between transepidermal water loss and the effective contact coefficient, which indicates skin barrier function and affected by skin surface electrolytes and reflects water content, in moisture meter analysis (r(2)=0.32, p<0.01). Transepidermal water loss returned to the control level at 1 year after healing with both dressings. The effective contact coefficient of the polyurethane wound was significantly lower than that of hydrogel at 1 month (p<0.01), while both dressing wounds demonstrated significantly higher values at both 1 month and 1 year compared to the control (p<0.01). The polyurethane dressing is therefore superior both clinically and in moisture meter analysis.

A basic fibroblast growth factor improved the quality of skin grafting in burn patients.

To avoid hypertrophic scars in burn wounds, the simultaneous application of basic fibroblast growth factor (bFGF) with regular surgical debridement and skin grafting was investigated for skin hardness by clinical examination and instrumental measurement. As little is known about the role of bFGF in wounds, burn wound scars were tested for hardness. Burn scars in various anatomical locations at least 1 year after final wound healing clinically demonstrated a significantly lower hard score in bFGF-treated wounds than in non-bFGF wounds (0.95+/-0.51 versus 2.3+/-0.66, respectively, p<0.01). In addition, a durometer, which is widely used in industry to measure materials similar to skin, such as rubber and thread-balls, demonstrated a significantly lower reading in bFGF-treated wounds than in non-bFGF wounds (7.9+/-3.64 versus 15.5+/-4.39, bFGF versus non-bFGF, respectively, p<0.01). The results demonstrated that burn wounds treated with clinically approved bFGF might contribute to a better cutaneous wound quality, at least in terms of hardness.

Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production.

BACKGROUND AND OBJECTIVE: The combined application of cytokines on embryonic fibroblasts and dermal substitute were studied for optimal skin defect coverage. The mechanism of combined treatment of leukemia inhibitory factor (LIF)-transfected embryonic fibroblasts and vascular endothelial growth factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute. METHODS: Mouse embryonic fibroblast cells, BALB-3T3, were stably transfected with mouse full-length LIF cDNA and added to various doses of VEGF for detection of signaling interaction. LIF-transfected cells and VEGF treatment were tested with pig-tendon derived collagen dermal substitute in the backs of BALB/c male mice up to for 14 days. RESULTS: LIF-transfected cells as well as vector-transfected fibroblasts significantly proliferated by 1, 10, or 100 ng VEGF on days 3 and 5. Erk mitogen-activated protein (MAP) kinase phosphorylation was observed from 1 to 30 min in LIF-transfected and 10 ng of VEFG, and 1 to 60 min in LIF-transfected and 100 ng VEFG treatments. The cellular fibronectin levels also increased in LIF-transfected cells with 10 and 100 ng VEGF additions. In in vivo analyses, LIF-transfected embryonic fibroblasts with 50 microg of VEGF markedly enhanced collagen I expression and CD34 angiogenic marker on days 7 and 14. CONCLUSION: LIF transfection and VEGF treatment enhanced phosphorylated-Erk-MAP kinase in vitro. In vivo study revealed that the combined application of LIF transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of a dermal substitute induced greater skin collagen production and angiogenesis in the dermal substitute.

Basic Fibroblast Growth Factor in Scarless Wound Healing.

SIGNIFICANCE: The benefit and role of basic fibroblast growth factor (bFGF) in scarless wound healing in clinical application and basic mechanism are discussed. bFGF is a glycoprotein which is widely used in treating wounds and ulcers. bFGF is easily applicable to any type of wound and leads to a better outcome in color, texture, and firmness. RECENT ADVANCES: The amniotic fluids from human mid-gestational trimester may play an important role in scarless wound healing. To investigate cell properties, we used amniotic fluid to augment both adult and fetal fibroblast mitogenic activities, including DNA synthesis and cell proliferation. Preincubation by both bFGF receptor blocker and anti-bFGF antibody significantly decreases proliferative activity in both adult and fetal skin fibroblasts. CRITICAL ISSUES: Adult wound healing, to some extent, demonstrates scar formation, leading to unfavorable clinical mismatch of tissue texture and color and causing stiffness. bFGF may improve the outcome of wound healing by normalizing the tissue texture and color to the adjacent intact skin and optimally enhancing wound healing. FUTURE DIRECTIONS: bFGF activates ERK and Akt phosphorylation in a dose-dependent manner in both adult and fetal skin fibroblasts, which suggests that bFGF in amniotic fluid plays the most major role in cell proliferation. Application of bFGF from an early wounding stage may lead to better fibroblast proliferation and DNA synthesis through the process of ERK/Akt phosphorylation.

Early experiences with stem cells in treating chronic wounds.

This review provides a thorough and clear discussion on the outcomes of stem cells in treating chronic wounds. With recent technological developments that now allow isolation and culture of stem cells, researchers are able to perform vigorous studies on somatic or adult stem cells. Human and animal stem cell studies are discussed with a focus on the basic process of stem cells in wound healing and the authors' first-hand clinical experience with stem cells used for chronic wound healing.

Mesenchymal stem cell therapy for cutaneous radiation syndrome.

Systemic and local radiation injuries caused by nuclear power reactor accidents, therapeutic irradiation, or nuclear terrorism should be prevented or properly treated in order to improve wound management and save lives. Currently, regenerative surgical modalities should be attempted with temporal artificial dermis impregnated and sprayed with a local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Human mesenchymal stem cells and adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and were tested for differentiation and local stimulation effects in the radiation-exposed wounds. The perforator flap and artificial dermal template with growth factor were successful for reconstruction in patients who were suffering from complex underlying disease. Patients were uneventfully treated with minimal morbidities. In the experiments, the hMSCs are strongly proliferative even after 20 Gy irradiation in vitro. In vivo, 4 Gy rat whole body irradiation demonstrated that sustained marrow stromal (mesenchymal stem) cells survived in the bone marrow. Immediate artificial dermis application impregnated with cells and the cytokine over the 20 Gy irradiated skin and soft tissues demonstrated the significantly improved fat angiogenesis, architected dermal reconstitution, and less inflammatory epidermal recovery. Detailed understanding of underlying diseases and rational reconstructive procedures brings about good outcomes for difficult irradiated wound healing. Adipose-derived stem cells are also implicated in the limited local injuries for short cell harvesting and processing time in the same subject.

Noncultured autologous adipose-derived stem cells therapy for chronic radiation injury.

Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years.

Human mesenchymal stem cells may be involved in keloid pathogenesis.

BACKGROUND: The pathogenesis of keloid is poorly understood. Although vigorous investigations have attempted to elucidate the mechanisms or causative factors of keloid, there are little data on why keloids are very intractable and recur easily in each patient. METHODS: In an attempt to analyze the possible interaction between human mesenchymal stem cells and keloid-derived fibroblasts, the dual-chamber cell-migration assay, cell proliferation, ultrastructural morphology, and Western blot analysis were used to investigate the production of the extracellular matrices of the coculture. RESULTS: Cell proliferation was not significantly different between keloid-derived fibroblasts and normal dermal fibroblasts during a 4-day observation period. There was a significant cell migration of human mesenchymal stem cells when keloid-derived fibroblasts were placed in the bottom chamber, compared to when normal dermal fibroblasts were placed in the same way in 8-microm diameter pore membranes (190.6 +/- 51.45 and 32.0 +/- 6.20 cells/field, respectively, P < 0.01). With 3-microm diameter pores, the human mesenchymal stem cells migrated in the pores only when the keloid-derived fibroblasts were placed in the bottom chambers (6.4 +/- 3.84 cells/field). Monolayer coculture of human mesenchymal stem cells and keloid-derived fibroblasts demonstrated further functional differentiation, such as collagen secretion and abundant rough endoplasmic reticulum. Western blot analysis of the cells in the modified dual-chamber culture demonstrated most significantly abundant fibronectin expression when the human mesenchymal stem cells contained keloid fibroblasts. CONCLUSION: The results of this study may indicate that human mesenchymal stem cells participate and recruit in keloid pathogenesis by differentiating themselves toward keloid recalcitrant formation and progression.