Biomedical subjects

Yoko Yamamoto

Publications and source records attributed to Yoko Yamamoto.

At least 37 records · Page 2Linked to original sources

PubMed2004

Engineering high-level aluminum tolerance in barley with the ALMT1 gene.

Acidity is a serious limitation to plant production on many of the world's agricultural soils. Toxic aluminium (Al) cations solubilized by the acidity rapidly inhibit root growth and limit subsequent uptake of water and nutrients. Recent work has shown that the ALMT1 gene of wheat (Triticum aestivum) encodes a malate transporter that is associated with malate efflux and Al tolerance. We generated transgenic barley (Hordeum vulgare) plants expressing ALMT1 and assessed their ability to exude malate and withstand Al stress. ALMT1 expression in barley conferred an Al-activated efflux of malate with properties similar to those of Al-tolerant wheat. The transgenic barley showed a high level of Al tolerance when grown in both hydroponic culture and on acid soils. These findings provide additional evidence that ALMT1 is a major Al-tolerance gene and demonstrate its ability to confer effective tolerance to acid soils through a transgenic approach in an important crop species.

Aluminum↗

PubMed2004

Effective accumulation of poly(vinylpyrrolidone-co-vinyl laurate) into the spleen.

To optimize polymer-conjugated drugs as a polymeric drug delivery system, it is essential to design polymeric carriers with tissue-specific targeting capacity. Previously, we showed that polyvinylpyrrolidone (PVP) was the most suitable polymeric carrier for prolonging the blood-residency of drugs, and was one of the best parent polymers to design the polymeric carriers with targeting capacity. In this study, we synthesized some hydrophobic PVP derivatives, poly(vinylpyrrolidone-co-styrene) [poly(VP-co-S)] and poly(vinylpyrrolidone-co-vinyl laurate) [poly(VP-co-VL)], and assessed their biopharmaceutical properties after intravenous administration in mice. The elimination of hydrophobic PVP derivatives from blood was the same as PVP, and the plasma half-lives of poly(VP-co-S) were almost similar to that of poly(VP-co-VL). Poly(VP-co-VL) efficiently accumulated in the spleen, whereas poly(VP-co-S) effectively accumulated in the liver. The level of poly(VP-co-VL) in the spleen was about 20 times higher than PVP and poly(VP-co-S). These hydrophobic PVP derivatives did not show any cytotoxicity against endothelial cells in vitro. Thus, poly(VP-co-VL) may be a useful polymeric carrier for drug delivery to the spleen. This study will provide useful information to design optimal polymeric carriers with targeting capacity to the spleen and liver.

Animals↗

PubMed2004

Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice.

Vitamin D metabolites influence the expression of various genes involved in calcium homeostasis, cell differentiation, and regulation of the immune system. Expression of these genes is mediated by the activation of the nuclear vitamin D receptor (VDR). Previous studies have shown that a hormonally active form of vitamin D, 1alpha,25-dihydroxyvitamin D3, exerts anticoagulant effects in cultured monocytic cells. To clarify whether activation of VDR plays any antithrombotic actions in vivo, hemostatic/thrombogenic systems were examined in normocalcemic VDR knock-out (KO) mice on a high calcium diet and compared with wild type and hypocalcemic VDRKO mice that were fed a regular diet. Platelet aggregation was enhanced significantly in normocalcemic VDRKO mice compared with wild type and hypocalcemic VDRKO mice. Aortic endothelial nitric-oxide (NO) synthase expression and urinary NOx excretions were reduced in hypocalcemic VDRKO mice, but not in normocalcemic VDRKO mice. Northern blot and RT-PCR analyses revealed that the gene expression of antithrombin in the liver as well as that of thrombomodulin in the aorta, liver and kidney was down-regulated in hypo- and normocalcemic VDRKO mice. Whereas tissue factor mRNA expression in the liver and kidney was up-regulated in VDRKO mice regardless of plasma calcium level. Furthermore, VDRKO mice manifested an exacerbated multi-organ thrombus formation after exogenous lipopolysaccharide injection regardless of the calcemic conditions. These results demonstrate that activation of nuclear VDR elicits antithrombotic effects in vivo, and suggest that the VDR system may play a physiological role in the maintenance of antithrombotic homeostasis.

Animals↗

PubMed2004

Design of a pH-sensitive polymeric carrier for drug release and its application in cancer therapy.

PURPOSE: In this study, to optimize the polymeric drug delivery system for cancer chemotherapy, we developed a new pH-sensitive polymeric carrier, poly(vinylpyrrolidone-co-dimethylmaleic anhydride) [PVD], that could gradually release native form of drugs with full activity, from the conjugates in response to changes in pH. We examined the usefulness of PVD as a polymeric drug carrier. EXPERIMENTAL DESIGN: PVD was radically synthesized with vinylpyrrolidone and 2,3-dimethylmaleic anhydride, which is known to be a pH-reversible amino-protecting reagent. Conjugates between PVD and other drugs, such as Adriamycin (ADR), were prepared under the slightly basic conditions (pH 8.5). The drug-release pattern and the antitumor activity of PVD were examined. RESULTS: At pH 8.5, the release of the drugs from the conjugate was not observed. In contrast, PVD could release fully active drugs in the native form in response to the change in pH near neutrality, and gradually released drugs at neutral pH (7.0) and slightly acidic pH (6.0). The drug-release pattern in serum was almost similar to that observed during these physiological conditions. The PVD-conjugated ADR showed superior antitumor activity against sarcoma-180 solid tumor in mice, and it had less toxic side effects than free ADR. This enhancement in the antitumor therapeutic window may be due to not only the improvement of plasma half-lives and tumor accumulation of ADR, but also its controlled and sustained release from the conjugates in vivo. CONCLUSIONS: These results indicate that PVD is an effective polymeric carrier for optimizing cancer therapy.

Animals↗

PubMed2004

Optimal site-specific PEGylation of mutant TNF-alpha improves its antitumor potency.

Recently, we created a lysine-deficient mutant tumor necrosis factor-alpha [mTNF-alpha-Lys(-)] with full bioactivity in vitro compared with wild-type TNF-alpha (wTNF-alpha), and site-specific PEGylation of mTNF-alpha-Lys(-) was found to selectively enhance its in vivo antitumor activity. In this study, we attempted to optimize this PEGylation of mTNF-alpha-Lys(-) to further improve its therapeutic potency. mTNF-alpha-Lys(-) was site-specifically modified at its N-terminus with linear polyethylene glycol (LPEG) or branched PEG (BPEG). While randomly mono-PEGylated wTNF-alpha (ran-LPEG5K-wTNF-alpha) with 5 kDa of LPEG (LPEG5K) had about only 4% in vitro bioactivity of wTNF-alpha, mono-PEGylated mTNF-alpha-Lys(-) [sp-PEG-mTNF-alpha-Lys(-)] with LPEG5K, LPEG20K, BPEG10K, and BPEG40K had 82%, 58%, 93%, and 65% bioactivities of mTNF-alpha-Lys(-), respectively. sp-LPEG-mTNF-alpha-Lys(-) and sp-BPEG10K-mTNF-alpha-Lys(-) had much superior antitumor activity to those of both unmodified TNF-alphas and ran-LPEG5K-wTNF-alpha, though sp-BPEG40K-mTNF-alpha-Lys(-) did not show in vivo antitumor activity. Thus, the molecular shape and weight of PEG may strongly influence the in vivo antitumor activity of sp-PEG-mTNF-alpha-Lys(-).

Animals↗

PubMed2004

Poly(vinylpyrrolidone-co-dimethyl maleic acid) as a novel renal targeting carrier.

Poly(vinylpyrrolidone-co-dimethyl maleic acid) (PVD) was found to have high renal-targeting capability and safety as a drug carrier. To optimize the renal drug delivery system using PVD, the relationship between the molecular weight of PVD and its renal accumulation were evaluated in mice by their intravenous injection. It was found that the molecular size of 6-8 kDa was associated with the highest renal accumulation. The specific bioactivity of PVD-conjugated superoxide dismutase (SOD) relative to that of unmodified SOD gradually decreased with an increase in the degree of modification to SOD with PVD6K. The conjugated SOD (L-PVD-SOD) with the molecular size of 73 kDa, which had comparable specific bioactivity with native SOD, showed longer plasma half-life than native SOD. About sixfold more L-PVD-SOD was distributed to the kidneys than native SOD 3 h after intravenous injection, whereas extensive PVD modification did not enhance the renal accumulation of SOD. This L-PVD-SOD effectively accelerated recovery from mercuric chloride-induced acute renal failure in vivo. These results suggest that L-PVD-SOD may be the optimal derivative as a potential therapeutic agent to various renal diseases.

Acute Kidney Injury↗

PubMed2004

Brain masculinization requires androgen receptor function.

Testicular testosterone produced during a critical perinatal period is thought to masculinize and defeminize the male brain from the inherent feminization program and induce male-typical behaviors in the adult. These actions of testosterone appear to be exerted not through its androgenic activity, but rather through its conversion by brain aromatase into estrogen, with the consequent activation of estrogen receptor (ER)-mediated signaling. Thus, the role of androgen receptor (AR) in perinatal brain masculinization underlying the expression of male-typical behaviors remains unclear because of the conversion of testosterone into estrogen in the brain. Here, we report a null AR mutation in mice generated by the Cre-loxP system. The AR-null mutation in males (AR(L-/Y)) resulted in the ablation of male-typical sexual and aggressive behaviors, whereas female AR-null homozygote (AR(L-/L-)) mice exhibited normal female sexual behaviors. Treatment with nonaromatizable androgen (5alpha-dihydrotestosterone, DHT) was ineffective in restoring the impaired male sexual behaviors, but it partially rescued impaired male aggressive behaviors in AR(L-/Y) mice. Impaired male-typical behaviors in ERalpha(-/-) mice were restored on DHT treatment. The role of AR function in brain masculinization at a limited perinatal stage was studied in AR(L-/L-) mice. Perinatal DHT treatment of females led to adult females sensitive to both 17beta-estradiol and DHT in the induction of male-typical behaviors. However, this female brain masculinization was abolished by AR inactivation. Our results suggested that perinatal brain masculinization requires AR function and that expression of male-typical behaviors in adults is mediated by both AR-dependent and -independent androgen signaling.

Androgen Receptor Antagonists↗

PubMed2004

MalphaNP acid, a powerful chiral molecular tool for preparation of enantiopure alcohols by resolution and determination of their absolute configurations by the (1)H NMR anisotropy method.

A novel methodology using a chiral molecular tool of MalphaNP acid (1), 2-methoxy-2-(1-naphthyl)propionic acid, useful for preparation of enantiopure secondary alcohols and determination of their absolute configurations by the (1)H NMR anisotropy method was developed; racemic MalphaNP acid (1) was enantioresolved with (-)-menthol, and the enantiopure MalphaNP acid (S)-(+)-(1) obtained was allowed to react with racemic alcohol, yielding a mixture of diastereomeric esters, which was clearly separated by HPLC on silica gel. By applying the sector rule of (1)H NMR anisotropy effect, the absolute configuration of the first-eluted MalphaNP ester was unambiguously determined. Solvolysis or reduction of the first-eluted MalphaNP esters yielded enantiopure alcohols.

Alcohols↗

PubMed2004

The use of PVP as a polymeric carrier to improve the plasma half-life of drugs.

To achieve an optimum drug delivery such as targeting or controlled release utilizing bioconjugation with polymeric modifier, the conjugate between drugs and polymeric modifiers must be designed to show desirable pharmacokinetic characteristics in vivo. In this study, we assessed the biopharmaceutical properties of various nonionic water-soluble polymers as polymeric drug carriers. Polyvinylpyrrolidone (PVP) showed the longest mean resident time (MRT) after i.v. injection of all nonionic polymers with the same molecular size. In fact, tumor necrosis factor-alpha (TNF-alpha) bioconjugated with PVP (PVP-TNF-alpha) circulated longer than TNF-alpha bioconjugated with polyethylene glycol (PEG-TNF-alpha) with the same molecular size. Each nonionic polymeric modifier showed a different tissue distribution. Dextran was accumulated in the spleen and liver. Polydimethylacrylamide (PDAAm) tended to distribute in the kidney. However, PVP showed the minimum volume of tissue distribution. These results suggested that PVP is the most suitable polymeric modifier for prolonging the circulation lifetime of a drug and localizing the conjugated drug in blood.

Animals↗

PubMed2004

The targeting of anionized polyvinylpyrrolidone to the renal system.

We reported that the co-polymer composed of vinylpyrrolidone and maleic acid selectively distributed into the kidneys after i.v. injection. To further optimize the renal drug delivery system, we assessed the renal targeting capability of anionized polyvinylpyrrolidone (PVP) derivatives after intravenous administration in mice. The elimination of anionized PVP derivatives from the blood decreased with increasing anionic groups, and the clearance of carboxylated PVP and sulfonated PVP from the blood was almost similar. But carboxylated PVP efficiently accumulated in the kidney, whereas sulfonated PVP was rapidly excreted in the urine. The renal levels of carboxylated PVP were about five-fold higher than sulfonated PVP. Additionally, carboxylated PVP was effectively taken up by the renal proximal tubular epithelial cells in vivo after i.v. injection. These anionized PVP derivatives did not show any cytotoxicity against renal tubular cells and endothelial cells in vitro. Thus, these carboxylated and sulfonated PVPs may be useful polymeric carriers for drug delivery to the kidney and bladder, respectively.

Animals↗

PubMed2004

The role of phosphorus in aluminium-induced citrate and malate exudation from rape (Brassica napus).

Exudation of organic anions is believed to be a common tolerance mechanism for both aluminium toxicity and phosphorus deficiency. Nevertheless, which of these stresses that actually elicit the exudation of organic anions from rape (Brassica napus L) remains unknown, and the combined effects of Al toxicity and P deficiency on rape have not been reported before. Therefore, in the current study, Brassica napus var. Natane nourin plants grown with or without 0.25 mM P were exposed to 0 or 50 micro M AlCl(3) and several parameters related to the exudation of organic anions from the roots were investigated. Eight days of P deficiency resulted in a significant growth reduction, but P deficiency alone did not induce exudation of organic anions. In contrast, Al strongly induced organic acid exudation, while simultaneously inhibiting root growth. Increased in-vitro activity of citrate synthase (CS, EC 4.1.3.7), malate dehydrogenase (MDH, EC 1.1.1.37) and phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31), together with reduced root respiration, indicated that the Al-induced accumulation and subsequent exudation of citrate and malate were associated with both increased biosynthesis and reduced metabolism of citric and malic acid. Phosphorus-sufficient plants showed more pronounced aluminium-induced accumulation and exudation of organic anions than P-deficient plants. A divided root chamber experiment showed the necessity of direct contact between Al and roots to elicit exudation of organic anions. Prolonged exposure (10 days) to Al resulted in a decrease in the net exudation of citrate and malate, and the rate of decrease was much more rapid in P-deficient plants than in P-sufficient plants. It is concluded that P nutrition affects the level of Al-induced synthesis and exudation of organic anions. However, the mechanism needs further investigation.

Journal Article↗

PubMed2004

A wheat gene encoding an aluminum-activated malate transporter.

The major constraint to plant growth in acid soils is the presence of toxic aluminum (Al) cations, which inhibit root elongation. The enhanced Al tolerance exhibited by some cultivars of wheat is associated with the Al-dependent efflux of malate from root apices. Malate forms a stable complex with Al that is harmless to plants and, therefore, this efflux of malate forms the basis of a hypothesis to explain Al tolerance in wheat. Here, we report on the cloning of a wheat gene, ALMT1 (aluminum-activated malate transporter), that co-segregates with Al tolerance in F2 and F3 populations derived from crosses between near-isogenic wheat lines that differ in Al tolerance. The ALMT1 gene encodes a membrane protein, which is constitutively expressed in the root apices of the Al-tolerant line at greater levels than in the near-isogenic but Al-sensitive line. Heterologous expression of ALMT1 in Xenopus oocytes, rice and cultured tobacco cells conferred an Al-activated malate efflux. Additionally, ALMT1 increased the tolerance of tobacco cells to Al treatment. These findings demonstrate that ALMT1 encodes an Al-activated malate transporter that is capable of conferring Al tolerance to plant cells.

Adaptation, Physiological↗

PubMed2004

Selective enhancer of tumor vascular permeability for optimization of cancer chemotherapy.

Clinical approach using tumor necrosis factor-alpha (TNF-alpha) as selective destruction against tumor endothelial cells and selective enhancer of tumor vascular permeability for effective accumulation of antitumor chemotherapeutic agents has attracted attention. However, the clinical application of TNF-alpha as a systemic antitumor agent has been limited because of toxic side-effects. To systemically use TNF-alpha as an antitumor agent and the selective enhancer of tumor vascular permeability, we assessed the usefulness of PEGylated TNF-alpha (PEG-TNF-alpha). PEG-TNF-alpha at a dose of 1000 JRU showed marked hemorrhagic necrosis in S-180 tumors without side-effects due to selective destruction of tumor vasculature, whereas wild-type TNF-alpha at a dose of 10,000 JRU showed a little hemorrhagic necrosis with severe side-effects. PEG-TNF-alpha induced the enhancement of tumor vascular permeability. The permeability was increased at 1 h, after an i.v. injection of PEG-TNF-alpha and returned to the basal level at 2 h. In addition, high molecular weight of PEG (molecular weight; 500K) accumulated in tumor tissue as well as low molecular weight of PEG (molecular weight; 12K). On the other hand, PEG-TNF-alpha didn't affect the permeability of normal tissue and inflammation site. This data suggested that PEG-TNF-alpha was useful agent as selective enhancer of tumor vascular permeability with safe.

Animals↗

PubMed2004

[The transintervertebral disc approach for educational practice of the neurolytic celiac plexus block].

BACKGROUND: The transintervertebral disc approach was proposed recently for percutaneous neurolytic celiac plexus block (NCPB). Its superior simplicity, reliability, as well as safety potentially overcome the technical hurdles of NCPB that may interfere with the practical use of this validated analgesic intervention for abdominal cancer pain. The present study was conducted to evaluate the effectiveness of the use of this approach in a resident education program for NCPB. METHODS: The clinical results of NCPBs conducted from January 2001 to September 2002 were examined comparing that performed by institutional residents with that by specialized physicians authorized by the Japanese Society of Pain Clinicians. The transintervertebral disc approach was used in all cases. Each resident completed NCPB under close supervision of the specialists. RESULTS: Twenty-four patients received NCPB during the study period. Seven residents randomly completed 12 procedures and 4 specialists did others. The duration of fluoroscopy to complete the procedure was 256+/-109 sec in the resident group and 392+/-194 sec in the specialist group (ns). Significant pain reduction was obtained immediately after NCPB in all patients without any intergroup difference. No critical complication was observed in each group. CONCLUSIONS: The transintervertebral disc approach can be used effectively and safely in educational practice of NCPB for less-trained physicians.

Abdominal Neoplasms↗

PubMed2003

An intracellular mechanism of aluminum tolerance associated with high antioxidant status in cultured tobacco cells.

An aluminum (Al) tolerance mechanism, together with oxidative stress tolerance, was investigated in an Al tolerant cell line (ALT301) and the parental Al sensitive cell line (SL) of tobacco. During Al exposure in a simple calcium solution for 24 h, Al triggered the evolution of a reactive oxygen species (ROS) in SL much higher than ALT301 [Plant Physiol. 128 (2002) 63]. Under the conditions, Al enhanced comparable rates of citrate secretion from both cell lines to the same extent. Al enhanced the gene expression of manganese superoxide dismutase (MnSOD) in both cell lines, but at a significantly higher rate in SL than in ALT301, and also enhanced the enzyme activity of MnSOD in both cell lines to nearly the same level. These results suggest that the extracellular chelation of Al with organic acids and MnSOD is not involved in the mechanism of Al tolerance of ALT301. ALT301 contained ascorbate (ASA) and glutathione (GSH) levels that were higher than SL under normal growth conditions. During 24 h of post-Al treatment culture in growth medium, but not during 24-h Al exposure in a simple Ca(2+) solution, lipid peroxidation was enhanced in SL much higher than in ALT301, and the average SL amounts of ASA and GSH were exhausted compared to ALT301. Pre-loading of ASA prior to Al treatment improved the growth of SL during the post-Al treatment culture. ALT301 also exhibited cross-tolerance to H(2)O(2), Fe(2+) and Cu(2+). Under these oxidant exposures, ALT301 contained lower levels of intracellular H(2)O(2) or lipid peroxides, and maintained higher amounts of ASA and GSH than SL. Taken together, we conclude that the accumulation of Al in cells enhances the peroxidation of lipids exclusively under growing conditions, and that the higher content of ASA and GSH in ALT301 than in SL seems to be in part responsible for the tolerance mechanism of ALT301 to Al by protecting cells from either lipid peroxidation or H(2)O(2) commonly enhanced by Al or other oxidants.

Adaptation, Physiological↗

PubMed2003

Synthesis and magnetic properties of heterometal cyclic tetranuclear complexes [Cu(II)LM(II)(hfac)]2 (M(II) = Zn, Cu, Ni, Co, Fe, Mn; H3L = 1-(2-hydroxybenzamido)-2-((2-hydroxy-3-methoxybenzylidene)amino)ethane; Hhfac = hexafluoroacetylacetone).

A series of heterometal cyclic tetranuclear complexes [Cu(II)LM(II)(hfac)](2) (M(II) = Zn (1), Cu (2), Ni (3), Co (4), Fe(5), and Mn (6)) have been synthesized by the assembly reaction of K[CuL] and [M(II)(hfac)(2)(H(2)O)(2)] with a 1:1 mole ratio in methanol, where H(3)L = 1-(2-hydroxybenzamido)-2-((2-hydroxy-3-methoxybenzylidene)amino)ethane and Hhfac = hexafluoroacetylacetone. The crystal structures of 2, 4, and [Cu(II)LMn(II)(acac)](2) (6a) (Hacac = acetylacetone) were determined by single-crystal X-ray analyses. Each complex has a cyclic tetranuclear Cu(II)(2)M(II)(2) structure, in which the Cu(II) complex functions as a "bridging ligand complex", and the Cu(II) and M(II) ions are alternately arrayed. One side of the planar Cu(II) complex coordinates to one M(II) ion at the two phenoxo and the methoxy oxygen atoms, and the opposite side of the Cu(II) complex coordinates to another M(II) ion at the amido oxygen atom. The temperature-dependent magnetic susceptibilities revealed spin states of S(M) = 0, 1/2, 1, 3/2, 2, and 5/2 for the Zn(II), Cu(II), Ni(II), Co(II), Fe(II), and Mn(II) ions, respectively. Satisfactory fittings to the observed magnetic susceptibility data were obtained by assuming a rectangular arrangement with two different g-factors for the Cu(II) and M(II) ions, two different isotropic magnetic exchange interactions, J(1) and J(2), between the Cu(II) and M(II) ions, and a zero-field splitting term for the M(II) ion. In all cases, the antiferromagnetic coupling constants were found for both exchange interactions suggesting nonzero spin ground states with S(T) = 2/S(M) - S(Cu)/, which were confirmed by the analysis of the field-dependent magnetization measurements.

Journal Article↗

PubMed2003

Suppressive function of androgen receptor in bone resorption.

As locally converted estrogen from testicular testosterone contributes to apparent androgen activity, the physiological significance of androgen receptor (AR) function in the beneficial effects of androgens on skeletal tissues has remained unclear. We show here that inactivation of AR in mice using a Cre-loxP system-mediated gene-targeting technique caused bone loss in males but not in females. Histomorphometric analyses of 8-week-old male AR knockout (ARKO) mice showed high bone turnover with increased bone resorption that resulted in reduced trabecular and cortical bone mass without affecting bone shape. Bone loss in orchidectomized male ARKO mice was only partially prevented by treatment with aromatizable testosterone. Analysis of primary osteoblasts and osteoclasts from ARKO mice revealed that AR function was required for the suppressive effects of androgens on osteoclastogenesis supporting activity of osteoblasts but not on osteoclasts. Furthermore, expression of the receptor activator of NF-kappaB ligand (RANKL) gene, which encodes a major osteoclastogenesis inducer, was found to be up-regulated in osteoblasts from AR-deficient mice. Our results indicate that AR function is indispensable for male-type bone formation and remodeling.

Androgen-Insensitivity Syndrome↗

PubMed2003

Incorporation of adult organ-derived endothelial cells into tumor blood vessel.

In this study, we attempted to assess the incorporable potential of vascular endothelial cells derived from adult organ blood vessels into tumor blood vessels. Two kinds of adult organ-derived vascular endothelial cells, human aorta endothelial cells (HAEC) and umbilical vein endothelial cells (HUVEC), were administered into murine tumors inoculated to SCID mice. Many human blood vessel networks were visualized in the murine tumors. These cells in solid tumor not only survived and proliferated, but also incorporated into tumor endothelium. These results suggest that adult organ-derived vascular endothelial cells possess the potential to form the neovascular network in various tissues such as vascular endothelial progenitor-like cells in vivo. We propose that these cells can be regarded as a congenic (autologous) vector for vascular regeneration cell therapy and tumor vascular targeting gene therapy.

Adult↗