Biomedical subjects

Lianhua Bai

Publications and source records attributed to Lianhua Bai.

5 recordsLinked to original sources

PubMed2006

Human mesenchymal stem cells signals regulate neural stem cell fate.

Neural stem cells (NSCs) differentiate into neurons, astrocytes and oligodendrocytes depending on their location within the central nervous system (CNS). The cellular and molecular cues mediating end-stage cell fate choices are not completely understood. The retention of multipotent NSCs in the adult CNS raises the possibility that selective recruitment of their progeny to specific lineages may facilitate repair in a spectrum of neuropathological conditions. Previous studies suggest that adult human bone marrow derived mesenchymal stem cells (hMSCs) improve functional outcome after a wide range of CNS insults, probably through their trophic influence. In the context of such trophic activity, here we demonstrate that hMSCs in culture provide humoral signals that selectively promote the genesis of neurons and oligodendrocytes from NSCs. Cell-cell contacts were less effective and the proportion of hMSCs that could be induced to express neural characteristics was very small. We propose that the selective promotion of neuronal and oligodendroglial fates in neural stem cell progeny is responsible for the ability of MSCs to enhance recovery after a wide range of CNS injuries.

Animals↗

PubMed2006

Identification and characterization of mouse cochlear stem cells.

Genetic, noise- and drug-induced loss of hair cells in the mouse and human cochlea leads to permanent hearing loss due to lack of regeneration of hair cells, which may be due to reduced numbers or loss of the regenerative ability of stem cells in the adult cochlea. We hypothesized that the mouse neonate cochlea harbors stem cells capable of differentiating into hair cells. Cells from the primary neonate cochlear culture began to proliferate and formed floating spheres after 14 days in vitro (DIV). By comparison, spheres from the primary culture of the cortex were observed after 7 DIV. Cochlear sphere cells could be passaged and the new spheres were observed after 7 DIV. Cochlear sphere cells were capable of differentiating into astrocytes and oligodendrocytes, but not neurons under the conditions tested. Cochlear sphere cells expressed Sox2 and Myo7a, but failed to show markers that are expressed exclusively in mature cochlear tissue, while cells from cortex spheres expressed Sox2 and Otx2, but not Myo7a. Our results show that cochleae from neonatal mice harbor cells capable of forming spheres and cells from these spheres appear to be better endowed to become hair cells.

Age Factors↗

PubMed2003

Efficient engraftment of human primary breast cancer transplants in nonconditioned NOD/Scid mice.

We describe a new human tumor xenotransplant animal model that is highly efficient for engraftment, does not need host conditioning and is suitable for in vivo studies of human tumors. Pieces of 61 freshly operated primary breast tumors were implanted into 172 irradiated and 228 nonconditioned NOD/Scid mice. A high mortality was observed in irradiated but not in nonconditioned recipients. More than 90% of analyzed implanted breast cancer specimens engrafted in the NOD/Scid mice irrespective of pretreatment. The tumors were vascularized within 3 days of implantation and maintained original histomorphology as well as expression patterns of tumor markers (cytokeratin and MUC1) and cytokines (tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and IL-10) released by adjacent stromal cells. A majority of tumors grew slowly, locally infiltrating host tissue, whereas some grew aggressively, developing large, fatal tumor masses and metastases within regional lymph nodes. Tumor progression in mice correlated with stage, grade, proliferation index and hormone receptor status of primary tumors. The reproducible growth behavior and preservation of characteristic features suggest that this new xenotransplant model is relevant and can be recommended for testing new anticancer therapies.

Animals↗

PubMed2003

Cognate interactions between memory T cells and tumor antigen-presenting dendritic cells from bone marrow of breast cancer patients: bidirectional cell stimulation, survival and antitumor activity in vivo.

Dendritic cells (DC) and T cells were generated from Ficoll separated bone marrow (BM) mononuclear cells of primary operated breast cancer patients according to new cell culture protocols. BM-DC were capable of functioning as professional antigen-presenting cells (APCs) and of inducing autologous antigen-specific memory T-cell responses to either tetanus toxoid recall antigen or to breast cancer antigens. Treatment with lipopolysaccharide (LPS) resulted in phenotypic and functional maturation of BM-DC. When BM-DC, pulsed with breast cancer-associated tumor antigens, were cocultured with autologous patient-derived BM-T cells to allow for cognate breast cancer antigen recognition and stimulation, apoptosis of T cells-which occurred in noncognate coculture systems-was inhibited. Furthermore, in cocultures allowing for antigen-specific cognate interactions, the expression on BM-DC of CD83, MHC class II, CD40 and CD86 molecules was upregulated and the cytokines IL-12 and IFN-alpha were produced in significantly elevated amounts. Adoptive transfer of breast cancer-reactive memory T cells together with APCs into human breast cancer-bearing NOD/SCID mice caused a regression of the tumor and prolonged survival of the animals. This was not the case when such animals had been treated by transfer of reactivated BM T cells without BM-DCs. Our findings suggest that cognate interactions between cancer patient-derived memory BM-T cells and tumor antigen-presenting BM-DCs are important for reciprocal cell stimulation, survival and therapeutic activity.

Animals↗

PubMed2003

Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer.

PURPOSE: Bone marrow is a special compartment for antitumor immunological memory in patients with breastcancer. Until now, the influence of adjuvant systemic therapy on the immune system has only been investigated in peripheral blood and not in bone marrow. In this study, we analyzed the effect of hormone therapy and chemotherapy on the immune activation status in bone marrow. EXPERIMENTAL DESIGN: In 34 patients with breast cancer, bone marrow was aspirated 24 months after primary surgery and adjuvant systemic therapy. The immune system of these patients was compared with that of patients at the time of primary surgery (n = 90). Three-color flow cytometry was used to identify the number and activation state of T cells, natural killer (NK) cells, monocytes/macrophages, and subsets by means of a panel of monoclonal antibodies. RESULTS: The proportion of all T cells was significantly lower in patients after adjuvant systemic therapy than in patients with primary breast cancer or normal healthy donors. Chemotherapy apparently had a particularly suppressive effect on naïve CD4 T cells and, to a lesser extent, on memory CD4 T cells. Hormone therapy apparently had a significant suppressive effect on both naïve and memory CD8 T cells. The numbers of NK cells (CD56) and of monocytes/macrophages (CD14) recovered rapidly after adjuvant chemotherapy. However, subpopulations with potential antitumor reactivity, such as activated NK and NK T cells, were reduced per long term after chemotherapy. CONCLUSIONS: These findings suggest profound and long-lasting negative effects on the bone marrow immune system by present day adjuvant therapy in breast cancer.

Bone Marrow Cells↗