Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance A historical overview of clinical applications of placental extracts, cells, and tissue components is described Empirically accumulated data are summarized and compared with modern research Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine

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Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects.

Improvement effects of a mixed extract of flowers of Pueraria thomsonii Benth. and peels of Citrus unshiu Markovich on postmenopausal symptoms of ovariectomized mice

The fatigue spreads among the people who live under stressful life and brings about a negative impact on physical function. Here we evaluated the anti-fatigue effects of fermented porcine placenta (FPP) and main constituents, lysine (Lys) and leucine (Leu) with treadmill stress test and forced swimming test (FST) in animal models. The mice were administrated with FPP, Lys, and Leu for 21 days. After treadmill exercise, FPP, Lys, and Leu significantly reduced fatigue-related biochemical parameters, including lactate, lactate dehydrogenase, glucose, creatine kinase, urea nitrogen, cortisol, and pro-inflammatory cytokines, whereas superoxide dismutase activity and glycogen levels were significantly increased by FPP, Lys, and Leu. In the FST, FPP, Lys, and Leu significantly decreased immobility times and up-regulated brain-derived neurotrophic factor expression in brain. Furthermore, FPP, Lys, and Leu significantly decreased production of tumor necrosis factor-α, interleukin (IL)-6, IL-1β, and IL-4 through blockade of caspase-1/nuclear factor-κB pathway in stimulated splenocytes. In addition, FPP, Lys, and Leu significantly promoted proliferation of splenocytes. In conclusion, these findings suggest the potential of FPP as a novel functional food for the regulation of fatigue.

Effect of fermented porcine placenta on physical fatigue in mice.

Recent studies have indicated that polysaccharides, the main component of the Lycium barbarum L. fruit, have beneficial effects (e.g., anxiolytic, antioxidant, and neuroprotective) on humans and rodents. However, the effects of different dosages of such polysaccharides on ovariectomized rats and their underlying mechanisms in the brain have not been evaluated in the literature. Here, we aimed to evaluate the effects of the high and low doses of polysaccharides obtained from Lycium barbarum fruits (HD-LBP and LD-LBP, respectively) on anxious behaviors via behavioral (using the OFT and EPM), biochemical (using ELISA), and immunohistochemical (using immunohistochemical staining) measures in detail. Two weeks after ovariectomy, the rats were randomly assigned to either the treatment conditions [control (DW, 3 mL/kg, p.o., per day), LD-LBP (20 mg/kg, 3 mL/kg, p.o., per day), HD-LBP (200 mg/kg, 3 mL/kg, p.o., per day), 17 β-ES (1 mg/kg, 3 mL/kg, p.o., per day), DZ(1 mg/kg, 3 mL/kg, p.o., per day)] or operation type [SHAM (pseudo-ovariectomized) and OVX (ovariectomized)]. The treatments were applied for 30 consecutive days, and then serum and brain tissue samples of all rats were collected. Biochemical (SOD, CAT, GPX, MDA, and 17 β-ES) and immunohistochemical (BDNF, SER, and apoptosis) analyses of the samples were performed as well. The rats administered HD-LBP and LD-LBP were less anxious than the control groups. The HD-LBP-treated rats had high levels of SOD and low levels of MDA in their serum samples. Moreover, HD-LBP and drug-treated groups had a high number of SER receptors and BDNF-positive cells and a low number of TUNEL-positive cells in their hippocampal brain tissues. The HD-LBP treatments decrease anxious behavior by increasing antioxidant enzyme activities, hippocampal SER and BDNF neurotransmitter levels and decreasing the TUNEL-positive cell count of ovariectomized rats. Given these findings, we suggest that menopause-induced symptoms of anxiety can be reduced by polysaccharides obtained from goji berry fruits, and that these findings will be beneficial for the production studies of natural herbal-origin antianxiety (anxiolytic) drugs in the future.

Anxiolytic, antioxidant, and neuroprotective effects of goji berry polysaccharides in ovariectomized rats: experimental evidence from behavioral, biochemical, and immunohistochemical analyses.

Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components. Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model. Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration. Conclusion: In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.

Highly elastic 3D-printed gelatin/HA/placental-extract scaffolds for bone tissue engineering

Menopause is a significant physiological phase that occurs as women's ovaries stop producing ovum and the production of estrogen declines. Human placenta and some amino acids are known to improve menopausal symptoms. In this study, we investigated that porcine placenta extract (PPE) and arginine (Arg), a main amino acid of PPE, would have estrogenic activities in ovariectomized (OVX) mice as a menopause mouse model, human breast cancer cell line (MCF-7) cells, and human osteoblast cell line (MG-63) cells. PPE or Arg significantly inhibited the body weight and increased the vagina weight compared to the OVX mice. PPE or Arg ameliorated the vaginal atrophy in the OVX mice. The levels of 17β-estradiol and the activities of alkaline phosphatase (ALP) were significantly increased by PPE or Arg in the serum of OVX mice. Trabecular bone parameters such as bone mineral density and porosity were also improved by PPE or Arg in the OVX mice. In the MCF-7 and MG-63 cells, PPE or Arg significantly increased the cell proliferation, estrogen receptor β mRNA expression, and estrogen-response elements luciferase activity. Finally, PPE or Arg increased the activations of ALP and extracellular signal-regulated kinase 1/2 in the MG-63 cells. These results indicate that PPE or Arg would have estrogenic and osteoblastic activity. Therefore, PPE or Arg may be useful as new pharmacological tools for treating menopausal symptoms including osteoporosis. Free Korean abstract: A Korean translation of this abstract is freely available at http://www.reproduction-online.org/content/150/3/173/suppl/DC1.

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Protective effect of porcine placenta in a menopausal ovariectomized mouse.

Static blood (SB) is a traditional Korean medicine disease symptom caused by a blood amassment, which refers to a pathological product of blood circulating poorly or accumulating in the interior. The growth and denaturalization of various organizations, inflammatory response and blood circulation disorder are regarded pathological conditions of SB. Endometrial hyperplasia (EH) is a state of excessive proliferation of the cells of the endometrium. Therefore, we suggest the EH mouse model as the experimental animal model of SB. Keywords static blood, traditional Korean medicine, experimental animal model, endometrial hyperplasia Static blood (SB) in traditional Korean medicine (TKM) SB is a pathological product of blood stagnation, including extravasated blood and the blood circulating sluggishly or blood congested in a viscus, all of which may turn into pathogenic factor, the same as blood stasis or stagnant blood. Major causes of SB are a blood heat, blood cold and bleeding caused by traumatic injury or others. Many classic medicine books introduced the symptoms of the SB are as follows; Pain (疼痛) (血證論, Tang rong chuan, 1884), chills (惡寒), fever (發熱), and alternating chills and fever (寒熱往來) (血證論, 名醫指掌·瘀血篇; 金匱要略, 婦人産後病篇, 婦人雜病篇, Zhang zhong jing, 217), abdomen fullness (腹部硬滿) (金匱要略, 驚悸吐衄篇; 讀醫隨筆, Zhou xue hai, 瘀血內熱, 1891), abdomen aggregation-accumulation (腹部積聚) (黃帝內經, Huang di, 168 BC), manic psychosis (發狂), depressive psychosis (癲狂), forgetfulness (善忘, 健忘) (傷寒論, Zhang zhong jing, 217; 諸病源候論, 卒被損瘀血候篇, Chao yuan fang, 610), thirst(口渴) (金匱要略, 驚悸吐衄下血胸滿瘀血病脈證治), bluish purple tongue and lip (靑紫舌), encrusted skin (肌膚甲錯) (諸病源候論, 卒被損瘀血候篇), etc. Although SB is a pathological product, formed SB causes various diseases including neuropsychiatric disorders (Kim, 2001), cardiovascular system disorder, musculoskeletal disorder (Lee et al., 2007), and obstetrics and gynecology diseases by disturbing blood circulation (Nam et al., 2006). Furthermore, the abnormal growth and denaturalization of various organizations and inflammatory response are regarded pathological conditions of SB.

A proposal for an experimental model of the static blood syndrome in the traditional Korean medicine

Arthritis is a major cause of joint pain, stiffness, and subsequent disability which adversely affects quality of life. Seriously, it can lead to long term social and psychological effects including loss of independence, depression, and anxiety. Arthritis is usually treated with joint replacement surgery or medications. However, the artificial joint is temporary and pharmacological measures have side effects, such as addiction or hypersensitivity. Thus, orthotics has been developed to improve arthritis as a nonpharmacological measure. The increased regional load across compartments of articular cartilage is an important factor in the cause of the arthritis. Mubal, a clinical shoe insole, has a sliding function to help people to walk straight and realign the body balance. The slide of Mubal reduces the knee joint loading in patients with arthritis. In addition, pumping function of Mubal can mitigate arthritis by stretching the squashed nerves from lumbar to cervical vertebral and actively circulating blood of pelvic limb. In addition, Mubal could help to stimulate the growth plate. Therefore, Mubal can be used for the child with short stature as well as patients with arthritis.

Chan-Lee Park

Papers

Protective effect of porcine placenta in a menopausal ovariectomized mouse.

A proposal for an experimental model of the static blood syndrome in the traditional Korean medicine

Useful effect of a clinical shoe insole, Mubal ® , as orthotics