Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

Rachakatla, Raja Shekar; Marini, Frank C.; Weiss, Mark L.; Tamura, Masaaki; Troyer, Deryl L.

doi:10.1038/sj.cgt.7701077

Cited by 122 publications

(127 citation statements)

References 33 publications

(40 reference statements)

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“…It has been shown convincingly that stem cells have the ability to traffic to tumors, and signals that mediate this effect seem to be similar or identical to those that mediate recruitment of stromal or defensive cells in tumors (1)(2)(3). There are also a number of reports showing that genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation (2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation

Ganta¹,

Doi²,

Ayuzawa³

et al. 2009

Cancer Research

110

112

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Genetically engineered stem cells efficiently deliver therapeutic proteins to cancer and other sites of inflammation. However, a major advantage would be realized if tumortrafficking stem cells that have not been genetically modified exhibit an inherent antitumor effect, thus circumventing the necessity of the expression of exogenous genes by the cells. We transplanted Fisher 344 rat-derived mammary adenocarcinoma cells (Mat B III) orthotopically into syngeneic F344 rats with an intact immune system. Rat umbilical cord matrix stem (rUCMS) cells derived from Wharton's jelly were then administered intratumoral (i.t) or i.v. 4 days later. The tumor attenuation effect was significantly evident starting from day 14 in i.v. and i.t. rUCMS cell-transplanted rats compared with sham-transplanted rats. In addition, unmodified rUCMS celltransplanted rats showed complete regression of tumors to undetectable levels by 34 to 38 days with no evidence of metastasis or recurrence 100 days post-tumor cell inoculation. Dye-loaded rUCMS cells were identified within tumors only 4 days after their i.v. transplantation. In vitro colony assays with rUCMS cells as feeder layers markedly reduced Mat B III colony size and number. Growth attenuation of Mat B III cells exposed to either rUCMS cells directly or to the conditioned medium derived from rUCMS cells was associated with apoptosis indicators, including increased activated caspase-3. In addition, rUCMS cells cocultured with Mat B III cells had a dose-dependent antiproliferative effect on Mat B III cells. These findings suggest that unmodified human UCMS cells could be used for targeted cytotherapy for breast cancer.

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Section: Introductionmentioning

confidence: 99%

Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation

Ganta¹,

Doi²,

Ayuzawa³

et al. 2009

Cancer Research

110

112

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“…They were engineered to express human interferon beta and were administered intravenously into SCID mice bearing tumours. This treatment significantly reduced the tumour burden (Rachakatla et al 2007). Similarly, human umbilical cord blood-derived MSCs (UCB -MSCs) have been used to deliver a secretable trimeric form of tumour necrosis factor-related apoptosis-inducing ligand (stTRAIL), via adenoviral transduction mediated by cell-permeable peptides, to human glioma cells in nude mice.…”

Section: Cancer Therapymentioning

confidence: 99%

Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues

Abdulrazzak

Moschidou

Jones

et al. 2010

J. R. Soc. Interface.

128

118

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Foetal stem cells (FSCs) can be isolated during gestation from many different tissues such as blood, liver and bone marrow as well as from a variety of extraembryonic tissues such as amniotic fluid and placenta. Strong evidence suggests that these cells differ on many biological aspects such as growth kinetics, morphology, immunophenotype, differentiation potential and engraftment capacity in vivo. Despite these differences, FSCs appear to be more primitive and have greater multi-potentiality than their adult counterparts. For example, foetal blood haemopoietic stem cells proliferate more rapidly than those found in cord blood or adult bone marrow. These features have led to FSCs being investigated for pre-and post-natal cell therapy and regenerative medicine applications. The cells have been used in pre-clinical studies to treat a wide range of diseases such as skeletal dysplasia, diaphragmatic hernia and respiratory failure, white matter damage, renal pathologies as well as cancers. Their intermediate state between adult and embryonic stem cells also makes them an ideal candidate for reprogramming to the pluripotent status.

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“…It thus appears that the cell fragment-mediated transfer of adenovirus is independent of adenovirus receptors and is not blocked by anti-adenovirus antibodies. Many studies of oncolytic virus-infected carrier cell systems have been reported in oncolytic HSV-1 mutant-infected PA-1 cells (7), in modified vaccinia virus-infected cytokine-induced killer (CIK) cells (11), in oncolytic adenovirus-infected A549 cells (15), in vesicular stomatitis virus (VSV)-infected colon carcinoma cells (13), in nerve growth factor-transduced autologous fibroblasts (19), and in human interferon ß-transduced umbilical cord matrix stem cell (20). In this study, AdE3-IAI.3B selectively killed OSCC cells in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells

Zhang

Hamada

Hyodo³

et al. 2011

Oncol Rep

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Abstract. Although replication-competent oncolytic viral vectors have been developed to improve antitumor activity, the generation of high titers of neutralizing antibodies inhibits repetitive viral infection. Many studies have reported that oncolytic virus-infected carrier cells can overcome this viral induced immunogenicity. However, the effects of oncolytic virus-infected carrier cells in human oral squamous cell carcinoma (OSCC) have not yet been examined. In the present study, simulating the clinical trial, we examined the antitumor activity of carrier cells infected with oncolytic adenovirus AdE3-IAI.3B in human OSCC. IAI.3B was highly activated in OSCC cells but not in normal cells. AdE3-IAI.3B killed OSCC cells in vitro but not normal cells. AdE3-IAI.3B-infected A549 carrier cells eradicated OSCC GFP-SAS tumors in nude mice. Anti-adenovirus neutralizing antibodies completely blocked the antitumor effect of AdE3-IAI.3B but did not block that of carrier cells. After the induction of anti-adenoviral CTL responses by immunization of adenovirus, administration of carrier cells induced complete regression of murine squamous cell carcinoma SCC7 tumors. Adenovirus-GM-CSF augmented the antitumor effect of carrier cells. The IAI.3B-driven oncolytic adenovirus-infected carrier cell system might prove useful in the treatment of OSCC and clinical trials of it should be conducted in the near future.

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Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

Cited by 122 publications

References 33 publications

Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation

Rat Umbilical Cord Stem Cells Completely Abolish Rat Mammary Carcinomas with No Evidence of Metastasis or Recurrence 100 Days Post–Tumor Cell Inoculation

Biological characteristics of stem cells from foetal, cord blood and extraembryonic tissues

Gene therapy for oral squamous cell carcinoma with IAI.3B promoter-driven oncolytic adenovirus-infected carrier cells

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