# Rejuvenation/Pregnancy specific biological substances
## Introduction

Some school of thoughts includes pregnancy under a chemical inflammation mediated by hormones and still some others believe pregnancy to be similar to neoplasm. One of the most important stages of embryo development in stem cell science is the inner cell mass stage of the blastocyst as this stage contains the three important germ layers namely, the ectoderm, mesoderm and endoderm along with the extra-embryonic part which gives rise to the placenta, amniotic sac, and the umbilical cord. The amniotic sac is a rich source of amniotic fluid which acts as a cushion for protecting the baby from bumps, injury, infection and helps in maintaining a constant temperature of the fetus. The amniotic membrane consisting of the chorion and the amnion. The placenta is the most important organ where it connects the fetus with the mother helping in the supply of oxygen, blood circulation, deliver essential growth factors and hormones for the development of the baby and by the end of pregnancy it passes antibodies so as to confer immunity to the fetus. other important functions include return of carbon dioxide, and other fetal waste products to the umbilical cord which are released in the mother’s bloodstream.
Placentophagy or eating of placenta is a well phenomenon observed among the animal kingdom and even in the case of herbivores like the cow. In traditional Chinese medicine, the placenta is often considered to be a very powerful healing medicine and is used in the form of dried version for medicinal purposes. Use of placenta has been documented over a century in Chinese system of medicine. The placenta is also used to ward off postpartum haemorrhage or post labor bleeding. Placental medicine can help in shortening the post bleeding time, restore the hormonal cycle, boost the immune system and increase lactation.In, 1910 for the first time Davis et al., used placenta membranes for skin transplantation followed by Sabella in 1913, where amniotic membrane was used for dressing and covering the burnt and ulcerated skin surfaces.The patients showed a marked improvement and since then, a new era in the field of dressing wounds started. In 1940, De Rotth first used placental membrane as a wound dressing model for ophthalmology in treating conjunctival epithelial defects. This paved the way for further use of placental membrane dressing in case of other ophthalmology defects.

## Mythology

Various stories of mythologies like the liver regeneration of Prometheus, Durga, and Raktajeeb is actually now a reality with regenerative medicine and cellular therapy strategies. Regenerative Medicine is that new branch of modern medicine which deals with the regeneration of degenerated organs, tissues and cells. Normally the classic natural example of regeneration in the biological world is pregnancy. Human curiosities regarding how pregnancy is mediated and how it survives in the hostile mother’s environment for 9 months is still a mystery and an active area of research pursuit among transplantation and developmental biologists.

## Details of the book

The book titled “Pregnancy Specific Biological substances” brings in about more than 70 distinguished and eminent professors working in the field of stem cell and regenerative medicine. Both Prof. Elaine Gluckman and the president of the Royal College of Physician, UK, Prof. Arul Kumaran has highlighted the important aspects and areas of research and treatment with pregnancy-specific biological substances. Dr. Ornella Parolini, an eminent stem cell scientist has further indicated the clinical significance and utility of these pregnancy-associated biological materials and a rich source for stem cells. Dr.Lin Huang and Prof. Andrew Burd of CUHK have indicated the massive global wastage of pregnancy specific biological substances and how it can be clinically utilized. In one of the chapters, Dr.Bon and Prof. Raudrant investigate the genetic factors associated with controlling the fetal growth, maternal nutrition factors, circulatory and hormonal placental factors. Prof. Pranke and Prof. Onsten discuss the utilization of cord blood transfusion, its strategies, immunology and its biochemistry. Prof. Robert Chow has discussed the utility of Hematopoietic stem cells from cord blood and its clinical use. Accounts of Dr.T.Brune and H.Garristen on the problems of autologous transfusion of placental/fetal blood to premature neonates have also been discussed at breadth. Dr. Shigeharu Hosono from Nihon University School of Medicine, Japan has also stated that the human cord blood transfusion can prevent the risk of transfusion-transmitted infections and suppress allogeneic reactions. Strategies of resuscitation can be also formulated by autologous transfusion of cord blood. Prof. Ende further outlines the efficiency of cord blood in case of disasters and wars. Other important chapters include finding a true substitute for adult blood transfusion by legendary Professor E.Moore from the University of Colorado, USA, who have further concluded that only blood can substitute blood. Use of Human Umbilical cord blood cells for treating stroke patients and their enormous potentialities in regenerative medicine have been mentioned in one of the chapters by Prof. Sanberg. Further, the editor of the book, Prof. Dr. Niranjan Bhattacharya and Dr.Abhijet Chaudhuri has reviewed the use of placental umbilical cord blood in the ischemic brain, a high concentration of fetal hemoglobin or HbF and its higher oxygen concentration compared to adult hemoglobin. Use of cord blood in Ophthalmology has been detailed in this book by Dr.Kyung-Chul Yoon, a pioneer in the field of Ophthalmology. An account of the use of placental umbilical cord in cardiovascular surgery has been mentioned by Yale School of Medicine professors Dr.Alan Dardik and Prof. Herbert Dardik. Prof. Robert Henning of The University of Florida, further discusses that the use of Human Umbilical cord blood cells can be used in case of myocardial infarction without the need for immune-suppressants as HUCBC has shown to significantly downregulate the inflammatory cytokines, neutrophils, CD3 and CD4 T-lymphocytes in heart with myocardial infarctions along with reduction in the myocardial infarct size. Clinically use of stem cells since, 2001 and its important effect in treating approaches have been highlighted by eminent stem cell scientist Prof. Amit Patel of The University of Pittsburg, Centre for Cardiac Cell Therapy and Mc Gowan Institute for Regenerative Medicine, USA. Dr. Jose Miguell of TCA Cellular Therapy, LLC, LA, a world known expert on mesenchymal stem cells has shared views on the ontogeny of multipotent hematopoietic stem cells and hemopoiesis.
The use and need of Human Umbilical Cord Blood derived hematopoietic stem cells and its superiority in terms of allogeneic bone marrow transplantation and its future and potential uses for curing auto-immune and bone marrow failures has been discussed by Jian-Xian Gao and Quansheng Zhou ,Department of pathology and Comprehensive Cancer Centre, Ohio State University along with Cyrus Tang of Soochow University and Department of Molecular Biology at the Scripps Institute, La Jolla, CA.
The chairman of Medistem Laboratories, Inc., California Dr Neil H.Riordan has mentioned that cord blood T cells produce significantly lower IFN-gamma, higher IL-10 upon activation with mature dendritic cells as against adult CD4 positive T cells. Further hyporesponsiveness was observed with respect to mitogen along with reduced level of LI-2 production and response to T cells. How stem cells survive and the importance of niche has also been noted by Prof. Ian MC Niece in this book.
Dr. Suzanne Watt, NBS, NHS, UK has cited their works pertaining to cord blood banking and storage on similar grounds to the New York Cord Blood Bank in the 1990’s and how these were established. Dr. Sabeen Askari has focused on total nucleated count or TNC an important parameter for cell dose and an important factor for HLA in donor choice. A threshold cell dose of >4 × 107 NC/kg at a collection and 3 × 107 NC/kg at infusion is recommended along with the correlation of CD34 positive cell count with engraftment where a dose of >2 × 105 CD34+ cells/kg is considered optimal. Due to the presence of inter-laboratory variability, there is a lack of standardization of counting method/protocol which has also been discussed in this book by Barker JN.
Problems pertaining to the collection of cord blood have been detailed by Dr.Pilar Solves and Dr. Vincete Mirabet of the Tissue Engineering Bank in Valencia. According to them, the quality of UCB is basically defined by three important parameters which are total nucleated count or TNC which is an important tool for cell dose evaluation, CD34 positive cells, and colony forming units or CFU’s meant for in vitro functionality assays of hematopoietic progenitors.
The World-renowned stem cell scientist Prof. Anthony Atala has also contributed in this book where he emphasized on the current potentialities and isolation of stem cells from amniotic fluid and amniotic membrane. Details of more than 100 clinical case studies by Prof. Dr. Niranjan Bhattacharya with patients suffering from diabetic foot ulcers and other nonhealing ulcers due to burn, HIV, gangrene and other background diseases and their effective wound dressing model with freshly collected properly screened amniotic membrane has been also detailed in this book. Further Peter Hollands, the architect of UK cord blood banks has detailed his opinion on endothelial progenitor cells or EPC derived from Human cord blood and their role in neovascularization in rat ischemic models. The expert idea on EPC’s by Italian scientist Dr.Maurizio Pesce from Milan has been further substantiated in this book. Dr.Shunichio Miyoshi of Keio University Medical School, Tokyo has shared that cardiomyocytes are terminal cells incapable of undergoing further division after birth and therefore in cases of ischemia these cardiomyocytes fail to undergo any cell division and can be restored only by exogenous stem cells. They have shown in the book that murine marrow-derived mesenchymal stem cells can convert into cardiomyocytes for the first time but fail to do so in case of humans which can be due to the fact that the human nucleus is much more protected than the murine ones from spontaneous mutations and tumor formation.
Other notable authors include Prof. David T Harris who has outlined the availability of multipotent stem cells in large numbers from cord blood and can be an alternative to hematopoietic and other sources of stem cells, Prof. Colin Mc Guckin, Prof. Zygmunt Pojda, Dr. Thomas Ichim who all have shared their views on the use of pregnancy specific biological substances and their utilities and basic science in stem cell medicine.
The book has received an immense positive review from Doody’s Book review, a medical library and medical books, papers and journals review and evaluation website by Bruce A. Fenderson on January 2012 where it is mentioned that the book is a fascinating snapshot of current research pertaining to pregnancy-specific biological medicine and stem cells meant for clinicians and basic science researchers. The book has also received 5 citations in high indexed stem cell and regenerative medicine journals and books published by Springer Verlag-London.

## Objective of the Book

The book is mainly meant for biomedical, medical students who want to update their knowledge in the field of regenerative medicine and the use of pregnancy specific biological substances in the field of stem cell therapies. Most of the true potentialities of these pregnancies specific biological substances have been ignored for some time. This book details the know-how, technology, and methods by which different stem cells can be utilized for treating diseases that are currently untreatable. The book encompasses areas of stem cell immunology, stem cell basics, animal and in vitro testing, quantification and validation and clinical cases. The book covers most of the diseases including their treatments with pregnancy-specific stem cells and is contributed by more than 50 renowned stem cell specialists and scientists. This book gives an overview of stem cell clinical and pre-clinical research that can benefit students and professionals who want to have a recent, updated and current view of stem cell and regenerative medicine.