Chong-Hyun Won

Systemic transplantation of human adipose stem cells attenuated cerebral inflammation and degeneration in a hemorrhagic stroke model

Adipose-derived stem cells (ASCs) are readily accessible multipotent mesenchymal stem cells and are known to secrete multiple growth factors, and thereby to have cytoprotective effects in various injury models. In the present study, the authors investigated the neuroprotective effect of ASCs in an intracerebral hemorrhage (ICH) model. ICH was induced via the stereotaxic infusion of collagenase, and human ASCs (three million cells per animal) isolated from human fresh fat tissue, were intravenously administered at 24 h post-ICH induction. Acute brain inflammation markers, namely, cell numbers positively stained for terminal transferase dUTP nick end labeling (TUNEL), myeloperoxidase (MPO), or OX-42, and brain water content were checked at 3 days post-ICH. In addition, the authors quantified brain degeneration by measuring hemispheric atrophy and perihematomal glial thickness at 6 weeks post-ICH, and determined modified limb placing behavioral scores weekly over 5 weeks post-ICH. The results showed that brain water content, TUNEL+, and MPO+ cell numbers were significantly reduced in the ASC-transplanted rats. ASC transplantation attenuated neurological deficits from 4 to 5 weeks post-ICH, and reduced both the brain atrophy and the glial proliferation at 6 weeks. Transplanted ASCs were found to densely populate perihematomal areas at 6 weeks, and to express endothelial markers (von Willebrand factor and endothelial barrier antigen), but not neuronal or glial markers. In summary, ASCs transplantation in the ICH model reduced both acute cerebral inflammation and chronic brain degeneration, and promoted long-term functional recovery.

Slowed Progression in Models of Huntington Disease by Adipose Stem Cell Transplantation

Adipose‐derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models.

Responses of adipose-derived stem cells during hypoxia: enhanced skin-regenerative potential

Mesenchymal stem cells within the stromal–vascular fraction of subcutaneous adipose tissue (i.e., adipose-derived stem cells (ASCs)), have been used for tissue engineering. In addition to serving a building-block function, ASCs are reported to secrete growth factors that are essential for their function. Increasing evidence indicates that ASCs play a significant role in skin regeneration, a function that is enhanced by hypoxia through upregulating secretion of growth factors. Although the anatomical sites of ASCs in the body are relatively oxygen-deficient, ASCs are usually cultured under normoxic conditions (i.e., atmospheric oxygen levels). Culturing ASCs under physiologically relevant low-oxygen-tension conditions may uniquely benefit the expansion, differentiation, adhesion, growth factor secretion and regenerative potential of ASCs. Therefore, understanding the response and adaptation of ASCs to hypoxia may be invaluable for developing novel cell- and cyto-therapy strategies. This review highlights our current understanding of cellular and molecular responses of ASCs to hypoxia, focusing on the enhancement of ASC function and secretory activity by hypoxic culture conditions.

Red Ginseng Root Extract Mixed with Torilus Fructus and Corni Fructus Improves Facial Wrinkles and Increases Type I Procollagen Synthesis in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study

Red ginseng contains many bioactive constituents, including various ginsenosides that are believed to have antioxidant, immunostimulatory, and anti-aging activities. Yet, no controlled human study has explored its effects on photoaged skin. This study determined whether long-term intake of a red ginseng extract-containing Torilus fructus and Corni fructus mixture reduces facial wrinkles and increases collagen synthesis in human skin. Healthy female volunteers over 40 years of age were randomized in a double-blind fashion to receive either red ginseng extract-containing herbal mixture at 3 g/day or placebo for 24 weeks. Facial wrinkles, elasticity, epidermal water content, erythema, and pigmentation were measured objectively. Facial skin samples were taken before and after treatment, and real-time polymerase chain reaction and immunohistochemical analyses were undertaken for expression of type I procollagen, matrix metalloproteinase (MMP)-9, and fibrillin-1, which are wrinkle-related biochemical markers. A total of 82 subjects completed the study. Facial wrinkles were significantly improved, type I procollagen gene and protein expression was increased, MMP-9 gene induction was prevented, and fibrillin-1 fiber length was elongated only in the treatment group. No changes were seen in the facial elasticity, epidermal water content, facial erythema and pigmentation, and epidermal thickness in either group. Thus a red ginseng extract-containing Torilus fructus and Corni fructus mixture improves facial wrinkles, a clinical sign of photoaging, and this improvement is associated with biochemical and histological evidence of increased collagen synthesis in the dermis. These results substantiate the alleged beneficial effects of red ginseng on photoaging and support its use as an effective beauty food.

Clinical and pathological characteristics of extradigital and digital glomus tumours: a retrospective comparative study.

Backgroundu2002 Most glomus tumours are located in the digits, especially in subungual areas. Less is known, however, about the clinical characteristics of extradigital glomus tumours.

Potential application of adipose-derived stem cells and their secretory factors to skin: discussion from both clinical and industrial viewpoints

Importance of the field: Adipose tissue is one of the richest sources of mesenchymal stem cells. Even more interesting is the fact that adipose-derived stem cells (ASCs) show an outstanding ability to regenerate damaged skin. Thus, ASCs are a popular and feasible treatment in clinical dermatology. Areas covered in this review: This review discusses the potential applications of ASCs and conditioned medium of ASC (ASC-CM) to skin, and briefly touches on the mechanisms by which ASCs promote skin regeneration. What the reader will gain: Clinically, processed lipo-aspirated (PLA) cells are commonly used for treatment of aged skin; however, the use of PLA cells for cosmetic purposes is not convenient, because PLA cells are prepared from patients. Alternatively, cosmetics that contain ASC-CM can be pre-made from healthy volunteers such that they are immediately available for clinical treatment of aged skin. Cell-based therapies are adequate for improvement of wrinkles or for soft tissue augmentation, whereas ASC-CM has merit for amelioration of skin tone. When culturing ASCs for the production of cosmetic raw materials, hypoxic culture conditions and transduction of specific genes into ASCs may increase the regenerative protein content of the conditioned medium. Take home message: Application of ASCs and ASC-CM to dermatology shows promising results for skin regeneration.

Neuroprotective effect of a cell-free extract derived from human adipose stem cells in experimental stroke models.

A recent study suggested that a cell-free extract of human adipose stem cells (hASCs-E) has beneficial effects on neurological diseases by modulating the host environment. Here, we investigated the effects of hASCs-E in several experimental models of stroke in vitro (oxygen and glucose deprivation, OGD) and in vivo (transient or permanent focal cerebral ischemia and intracerebral hemorrhage, ICH). Ischemia was induced in vitro in Neuro2A cells, and the hASCs-E was applied 24h before the OGD or concurrently. Focal cerebral ischemia was induced by unilateral intraluminal thread occlusion of the middle cerebral artery (MCA) in rats for 90min or permanently, or by unilateral MCA microsurgical direct electrocoagulation in mice. The ICH model was induced with an intracerebral injection of collagenase in rats. The hASCs-E was intraperitoneally administered 1h after the stroke insults. Treatment of the hASCs-E led to a substantially high viability in the lactate dehydrogenase and WST-1 assays in the in vitro ischemic model. The cerebral ischemic and ICH model treated with hASCs-E showed decreased ischemic volume and reduced brain water content and hemorrhage volume. The ICH model treated with hASCs-E exhibited better performance on the modified limb placing test. The expression of many genes related to inflammation, immune response, and cell-death was changed substantially in the ischemic rats or neuronal cells treated with the hASCs-E. These results reveal a neuroprotective role of hASCs-E in animal models of stroke, and suggest the feasible application of stem cell-based, noninvasive therapy for treating stroke.

A cell-free extract from human adipose stem cells protects mice against epilepsy

Purpose:u2002 Stem cell–based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs‐E) in a mouse model of epilepsy.

Differential Effects of Low-Dose and High-Dose Beta-Carotene Supplementation on the Signs of Photoaging and Type I Procollagen Gene Expression in Human Skin in vivo

Background: Although the photoprotective effects of β-carotene are thought to originate from its antioxidant properties, some studies documented pro-oxidant effects of β-carotene. Objective: Our purpose was to determine the effects of 2 different doses of dietary β-carotene on wrinkles and elasticity, procollagen gene expression and ultraviolet (UV)-induced DNA damage in human skin. Methods: Thirty healthy female subjects over the age of 50 years were randomized and received 2 different doses (30 and 90 mg/day) of β-carotene for 90 days. The baseline status was used as control. At baseline and completion of the study, facial wrinkles and elasticity were measured objectively. Buttock skin was taken to determine the type I procollagen, matrix metalloproteinase-1 and fibrillin-1 mRNA levels, and UV-induced thymine dimer and 8-hydroxy-2′-deoxyguanosine formation. Results: β-Carotene improved facial wrinkles and elasticity significantly only in the low-dose group. The minimal erythema dose decreased significantly only in the high-dose group. Type I procollagen mRNA levels were significantly increased to 4.4 ± 1.6 times the baseline level only in the low-dose group, and procollagen immunostaining increased accordingly. UV-induced thymine dimer staining was reduced in the low-dose group but tended to increase in the high-dose group. 8-hydroxy-2′-deoxyguanosine staining was significantly reduced in the low-dose group. Conclusions: 30 mg/day of β-carotene supplementation is demonstrated to prevent and repair photoaging.

Multipotent PDGFRβ-expressing cells in the circulation of stroke patients

Tissue pericytes respond to injury, and support vascular and tissue regeneration. The presence of pericytes in the circulation may provide an attractive framework for tissue regeneration. Here, we detected multipotent pericyte-like cells in the circulating blood and determined its profiles during cerebral ischemia. Pericyte-like cells were isolated from the peripheral blood of acute stroke patients or asymptomatic individuals with vascular risk factors by fluorescence or magnetic activated cell sorting with anti-PDGF receptor-beta (PDGFRβ) antibody. The morphologic and molecular features of circulating PDGFRβ(+) cells were compared with tissue pericytes, and the associations with respect to quantity in the blood, culture outcome, and patient characteristics were analyzed. We found an increase in circulating PDGFRβ(+) cells in acute stroke patients compared to controls and a correlation with neurologic impairment. The isolated PDGFRβ(+) cells expressed mesenchymal stem cell markers, proliferated, and were multipotent under permissive culture conditions. The multipotent nature of these cells was comparable to fat-derived PDGFRβ(+) cells. These cells could be obtained by pharmacologic stimulation using bone marrow mobilizer. Circulating PDGFRβ(+) cells will be useful for future research involving endogenous recovery or autologous cell-based therapy.