Stem Cell Research Articles

Excerpts of articles by Dr. Norman Ende and his colleagues.
The primary focus is stem cell research.  

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NOD-LtJ Type 1 Diabetes In Mice And The Effect Of Stem Cells – Berashis – Derived From Human Umbilical Cord Blood

NOD-LtJ Type 1 Diabetes In Mice And The Effect Of Stem Cells (Berashis) Derived From Human Umbilical Cord Blood

Norman Ende, Ruifeng Chen, and Richard Mack

Department of Pathology and Laboratory Medicine
New Jersey Medical School
185 South Orange Avenue, MSB-C501
Newark, NJ 07103

(Printed in Journal Of Medicine, Volumes 1-4, 2002)

Key Words: Berashis cell, cord blood, diabetes, NOD/LtJ mice, stem cell

[There is evidence that very immature pleuropotential stem cells – Berashis cells – exist in human umbilical cord blood in small numbers. We feel that these Berashis cells may have similar physiological properties to those attributed to embryonic stem cells. By administering megadoses of human umbilical cord blood mononuclear cells – thus increasing the number of Berashis cells administered – we were able to ameliorate disease and improve the lifespan of NOD/LtJ type 1 diabetic mice.]

Previously we have successfully delayed the onset of vasculitis and death in MRL Lpr/Lpr mice that are considered to have an autoimmune disease similar to human lupus erythematosus.

Likewise, with the use of megadose human umbilical cord blood mononuclear cells, we were able to delay the onset of symptoms and death in SOD1 mice that carry a transgene for amyotrophic lateral sclerosis, considered by some to be an autoimmune disease.

A similar approach was utilized with NOD/LtJ type 1 diabetic mice. By administering megadoses of human umbilical cord blood mononuclear cells, we were able to ameliorate the disease, and improved the life span. This occurred to a greater extent than with bone marrow obtained from congenic mice.

No immunosuppression was utilized in this study.

This study raises the possibility of utilizing human cord blood mononuclear cells in conjunction with pancreatic islet transplantation.

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Commentary – Berashis Cells In Human Umbilical Cord Blood Vs Embryonic Stem Cells

Commentary – Berashis Cells In Human Umbilical Cord Blood Vs Embryonic Stem Cells

Norman Ende
Professor of Pathology and Laboratory Medicine
UMDNJ-New Jersey Medical School
185 South Orange Avenue
Newark, NJ 07103

(Printed in Journal Of Medicine, Volumes 1-4, 2002)

Key Words: Berashis cells, cord blood, embryonic stem cell, human cord blood, therapeutic potential

[Since 1990 we have been aware that human umbilical cord blood had unique cells that displayed reparative ability for various organs in subject mice. We call these cells “Berashis Cells” – beginning cells – to distinguish them from embryonic stem cells, fetal stem cells, adult stem cells, or organ specific stem cells. While much public attention has been given to embryonic stem cell research, this article demonstrates that Berashis Cells from umbilical cord blood have the potential to attain similar  therapeutic  results.]

Over the past 3 years there have been numerous articles in medical journals, biological journals, and the lay press concerning the great potential of embryonic stem cells (Weissman, 2002). This has provoked extensive controversies, ethical, political, patient rights, attracting numerous television and press reports.

Throughout these articles, the potential for some of the cells found in cord blood collected from normal infants has been essentially ignored. Even though these human cells have been demonstrated to be therapeutically effective both in non-transgenic animal models and in transgenic models, including such diverse diseases as a mouse model for human lupus erythematosus to transgenic mice for Huntington disease, little attention has been paid to this subject.

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The Berashis Cell – A Review – Is It Similar To The Embryonic Stem Cell?

The Berashis Cell: A Review
Is It Similar To The Embryonic Cell

Norman Ende

Department of Pathology and Laboratory Medicine
New Jersey Medical School
185 South Orange Avenue, MSB-C501
Newark, NJ 07103

(Printed in Journal Of Medicine, Volumes 3 and 4, 2000)

Key Words: Berashis cells, embryonic stem cell, human cord blood
Abbreviations: HLA = Human lymphocyte antigen, SLE = systemic lupus erythematosis

Introduction

This article is an attempt to define very primitive pleuripotential and probably totipotential primitive cells found in umbilical cord blood and their clinical significance.

For lack of a better name, and in an effort to separate it from other “stem” cells, we have called it the “Berashis Cell” meaning “in the beginning” (בראשית) (Ende, 1995). Currently, we believe this cell exists in limited numbers in human umbilical cord blood, has never impacted on stroma, probably has some functional capacity at 4 degrees Celsius, and has few if any recognition antigens.

In its functional capacity it may be similar to that predicted for the embryonic stem cell derived from a fetus or embryos (Gerhart, 1998)

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Collection Of Umbilical Cord Blood For Transplantation

CORRESPONDENCE: COLLECTION OF UMBILICAL CORD BLOOD FOR TRANSPLANTATION
Letter to Editor from Dr. Norman Ende, M.D.
Published in: Blood, Vol80, No 6 (September 15), 1992: pp 1623-1631

To the Editor:

The article by Wagner et al was very encouraging on the potential use of human umbilical cord blood. On page 1879, 1st column 2nd paragraph, there appears a sentence that raises considerable legal, ethical, and medical questions, similar to what occurred in our studies approximately 25 years ago. The statement, which read, “However, recent alterations in the technique of cord blood collection (eg, earlier clamping of the cord) routinely yield twofold to fourfold larger harvest (ie, 150 to 300 mL),” raises considerable concern.

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Murine Survival Of Lethal Irradiation With Use Of Human Umbilical Cord Blood

Murine Survival Of Lethal Irradiation With Use Of Human Umbilical Cord Blood

Norman Ende, Nicholas M. Ponzio, Raghbir S. Athwal, Milton Ende, Dennis C. Giuliani

UMDNJ-New Jersey Medical School
Departments of Laboratory Medicine & Pathology; Microbiology and Molecular Genetics; Medicine – Hematology Division; Southside Regional Medical Center, Petersburg, VA

Summary

We have found that human umbilical cord blood (HUCB) will routinely protect mice exposed to lethal levels of irradiation. At the end of 50 days, over 70% of mice injected with HUBC survived 900 cGy of irradiation, which produced 100% deaths in the uninjected control animals.

Moreover, there was some evidence that human colony stimulating factors further improved survival. Anti-Natural Killer cell (NK) antibody was utilized along with HUCB in these studies, however, Anti-NK cell serum alone had no radioprotective effect in mice. The studies reported here suggest the possibility of utilizing HUCB for immediate protection of humans from lethal irradiation.

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Spotlight On Cord Blood Transplant Reminds Them Of A VA Med First

Spotlight On Cord Blood Transplant
Reminds Them Of A VA Med First

Letters To The Editor – Virginia Medical Quarterly 1990;117:282

Considerable recent attention has been given to the use of umbilical cord blood for bone marrow transplantation by the medical literature as well as the lay press and television. This letter is written to address the fact that it was the Virginia Medical Monthly that published the original article on this usage in 1972 and raised the possibility of umbilical cord blood banks.

The clinical work was performed in Petersburg, VA, and the laboratory studies in Atlanta, GA. The article reported a patient with acute lymphoblastic leukemia who obtained a documented temporary graft following administration of a relatively small quantity of umbilical cord blood matched only for ABO typing.

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Production Of Human To Mouse Xenografts By Umbilical Cord Blood

Production Of Human To Mouse Xenografts
By Umbilical Cord Blood

Norman Ende, Dennis Giuliani
Milton Ende, Nicholas M. Ponzio

Department of Pathology
University of Medicine and Dentistry of New Jersey
New Jersey Medical School, Newark, NJ 07103

(Received in final form March 2, 1990)

Utilizing human umbilical cord blood, it has been possible to create in irradiated animals a human to mouse xenograft. To facilitate hematopoietic reconstitution, SJL/J mice, which are functionally low in natural killer (NK) cells, were treated with anti-Asialo GM antibodies (anti-NK) and irradiation prior to injection of cord blood mononuclear cells.

In contrast, SJL/J mice with the “beige” (bg/bg) mutation, which confers a functional NK cell deficiency, required only irradiation for successful transplantation. Human cells, detected by means of DNA probes, were demonstrated in the lungs and lymph nodes of irradiated animals up to 6 months after injection of the human cord blood cells.

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Fetal Cord Blood’s Potential For Bone Marrow Transplantation

Fetal Cord Blood’s Potential For
Bone Marrow Transplantation

Norman Ende, Pranela Rameshwar, Milton Ende

Department of Pathology and Medicine,
Division of Hematology,
University of Medicine and Dentistry Of New Jersey
New Jersey Medical School, Newark, NJ 07103

(Received in final form April 17, 1989)

Approximately 18 years ago, the authors were able to produce an apparently successful bone marrow transplant by using umbilical cord blood. In view of the Chernobyl disaster and the subsequent problems of treatment with marrow transplantation, this study undertook to explore further the potential use of umbilical cord blood as a source of marrow cells.

Specimens of umbilical cord blood were collected from 13 routine obstetrical deliveries. All specimens grew erythroid and granulocytic-monocytic colonies. The formation of these various hematopoietic colonies from umbilical cord blood was at least equivalent to bone marrow, and in some instances over 5 times more effective.

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Hematopoietic Transplantation

Hematopoietic Transplantation by Means of
Fetal (Cord) Blood
A New Method

Milton Ende, M.D
Petersburg, Virginia

N. Ende, M.D.
Newark, New Jersey

A series of eight transfusions consisting of 30 to 85 ml of umbilical cord blood was utilized to establish a hematopoietic transplant in a patient with acute lymphoblastic leukemia on conventional therapy.

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Lymphangiosarcoma

Lymphangioscarcoma

Report of a Case
Milton Ende, M.D.
Petersburg, Virginia

In 1948, Stewart and Treves described a new type of neoplasm beginning in edematous extremities following radical breast surgery. Since the initial case report, 75 patients have been described. Of this number, those having interscapulo thoracic amputation had the best results. Of 25 cases, 5 were living 1 to 11 years postoperative. Only 2 of 18 who had radiotherapy are alive; 1, 2 years after treatment, and 1, 12 years. All 13 who had wide excision and irradiation expired. Ten had amputation of the arm and of these 1 was alive 51 months following surgery. All 10 who had no specific treatment were dead within 1 year.

The following case concerns a patient who had interscapulo thoracic amputation and various other modalities of therapy, including one unique approach.

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