Functional Activation of Autologous Human Diabetic Stem Cells for Cell Therapy

Diabetic retinopathy (DR) is a common cause of vision loss and blindness. Healthy CD34+ stem cells are capable of homing to vascular lesions and facilitating vascular repair. However, many diabetic patients have dysfunctional CD34+ stem cells with no reparative potential. CD34+ dysfunction is corrected by transiently inhibiting endogenous transforming growth factor-β1 (TGF-β1) within the patient’s own dysfunctional CD34+ stem cells using phosphorodiamidate morpholino oligomers (PMOs). Antisense TGF-β1-treated dysfunctional CD34+ stem cells are now functional, no longer require growth factor stimulation to evade apoptosis, and are stable at 37°C ex vivo for >5 days. We identified three markers of restored stem cell function: (1) upregulation of CXCR4 expression necessary for stem cell homing and adhesion, (2) SDF-1-mediated nitric oxide (NO) production required for cell mobility, and (3) restoration of the ability of CD34+ cells to migrate and repair vascular lesions. The antisense targets autocrine TGF-β expression, whereas neutralizing antibodies do not. The PMO antisense triggers a cascade of hematopoietic proliferation and differentiation that paracrine TGF-β cannot alter. We describe optimal PMO manipulation of CD34+ stem cells ex vivo for transplantation, screening multiple gene targets leading to the identification of TGF-β1, and a lead TGF-β1 inhibitor evaluated in clinical studies

Neurohistological basis for the functioning of paired half-centers

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49962/1/901010208_ftp.pd

The cytological structure of the human chorionic villus and decidua parietalis

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/49604/1/1000740302_ftp.pd

No evidence for selective follicle abortion underlying primary sex ratio adjustment in pigeons

Primary sex ratio adjustment in birds has been extensively studied, yet the underlying physiological mechanisms are far from understood. Avian females are the heterogametic sex (ZW), and the future sex of the offspring is determined at chromosome segregation during meiosis I, shortly before the oocyte is ovulated. Assuming that the mother can detect the sex of the developing oocyte before ovulation, it has been suggested that a follicle of the un-preferred sex could selectively be induced to become atretic and regress instead of being ovulated (selective follicle abortion). This potential mechanism has been proposed to underlie biased primary sex ratios in birds, including the homing pigeon (Columba livia domestica), which produces a modal clutch size of two eggs. However, without replacement by an additional, already mature follicle, abortion of a preovulatory follicle would most likely result in either reduced clutch sizes or laying gaps, since a not-yet-recruited follicle still needed to undergo the whole maturation phase. In the current study we killed female pigeons, which were adjusting embryo sex of first eggs according to change in body mass. We examined ovaries for signs of follicle abortion but did not find any supporting evidence. All females produced one or two mature follicles but only two out of the 56 experimental birds produced an additional third mature follicle. Therefore, our results do not corroborate the hypothesis that pigeon mothers manipulate primary offspring sex by selectively aborting follicles of the un-preferred sex

Apoptosis and proliferation in the trigeminal placode

The neurogenic trigeminal placode develops from the crescent-shaped panplacodal primordium which delineates the neural plate anteriorly. We show that, in Tupaia belangeri, the trigeminal placode is represented by a field of focal ectodermal thickenings which over time changes positions from as far rostral as the level of the forebrain to as far caudal as opposite rhombomere 3. Delamination proceeds rostrocaudally from the ectoderm adjacent to the rostral midbrain, and contributes neurons to the trigeminal ganglion as well as to the ciliary ganglion/oculomotor complex. Proliferative events are centered on the field prior to the peak of delamination. They are preceded, paralleled and, finally, outnumbered by apoptotic events which proceed rostrocaudally from non-delaminating to delaminating parts of the field. Apoptosis persists upon regression of the placode, thereby exhibiting a massive “wedge” of apoptotic cells which includes the postulated position of the “ventrolateral postoptic placode” (Lee et al. in Dev Biol 263:176–190, 2003), merges with groups of lens-associated apoptotic cells, and disappears upon lens detachment. In conjunction with earlier work (Washausen et al. in Dev Biol 278:86–102, 2005) our findings suggest that apoptosis contributes repeatedly to the disintegration of the panplacodal primordium, to the elimination of subsets of premigratory placodal neuroblasts, and to the regression of placodes

Macrophage Activation and Differentiation Signals Regulate Schlafen-4 Gene Expression: Evidence for Schlafen-4 as a Modulator of Myelopoiesis

Background: The ten mouse and six human members of the Schlafen (Slfn) gene family all contain an AAA domain. Little is known of their function, but previous studies suggest roles in immune cell development. In this report, we assessed Slfn regulation and function in macrophages, which are key cellular regulators of innate immunity

Studies on germ cells. I. The history of the germ cells in insects with special reference to the Keimbahn-determinants. II. The origin and significance of the Keimbahn-determinants in animals

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50235/1/1050250302_ftp.pd