Fetal tissue transplantation in Regenerative Medicine

Objectives of the book
Medical science is an extremely dynamic field aimed at making improvements in patients life through the course of newer developments. One of the most upcoming perhaps the most futuristic medicine of our era is the advent of Regenerative Medicine and stem cells. Regenerative Medicine is one of those areas focussed on the rejuvenation and regeneration of the failed organ and used in cases of irreversible damages to the body when all treatment options have failed.

Globally currently most of the medical labs are focussed on the use of stem cells in regeneration. Sources of stem cells like from an aborted normal fetus collected ethically or from pregnancy specific biological substances like the placental tissue, amniotic fluid, amniotic membrane, cord blood, Wharton’s Jelly have a milieu of cytokines, growth factors and is considered to be a hub for extremely potent stem cells that can aid in regeneration and healing.

Cell therapy is the main constituent of stem cell and regenerative medicine. Fetal tissue, for example, is one such extremely potent source which contains different and varying grades of stem cells in both differentiated and undifferentiated states. Also, another important content of this fetal tissue, these are highly hypo-antigenic depending upon its gestational stage as in early gestation period HLA’s are still not expressed and therefore can be transplanted without any major GVHD or immune rejection problems after a proper screening of the tissues for different infectious diseases. The fetal tissue microenvironment is a very protective one and such is its degree of protection that even in an allogeneic host even after 10 years, the fetal tissue transplanted was retrieved without any gross morphological changes with persistence of a group of primitive progenitor cells thereby eliciting another important mechanism that the efficacy of fetal tissue transplantation is not always mediated through cell transmigration and might be an important role played by the cytokines and growth factors secreted from the transplanted fetal tissue also. This method of transmigration of cells and soluble secreted factors like growth hormones and cytokines play an important role in healing and regeneration of diseases that might not respond to normal treatment methods and one of the main advantages of fetal tissue therapy is that it can easily be placed in a highly vascular area like the axilla which requires minimally invasive procedures.

Although Fetal tissue transplantation is not an entirely a new field of regenerative medicine and cell therapy, it has drawn some ire and attention from various religious and activists group as the method involves the use of aborted fetus which many religion considers the fetus a life even after it has been aborted. Surgically and ethically aborted fetus is one of the main sources of fetal highly potent stem cells, progenitor cells, stem cell-like cells and other multipotent adult stem cells in or out of transition with a huge potential in the treatment of degenerative diseases like Parkinson’s Disease, Alzheimer’s diseases, Multiple sclerosis, cirrhosis liver burn and non-healing ulcers just to name a few.

Chapters of the Book
The book is mainly dedicated and is written with a view to salute the pioneer of Reproductive Medicine and in vitro fertilization specialist, the legendary professor and scientist and the 2011 Nobel Prize recipient, Sir Robert Geoffrey Edwards, CBE, FRS who published the first multi-authored edition book on Human fetal and its application in transplantation medicine in 1992. Since then regenerative medicine and stem cell therapy have come a long way with many crucial changes both positive and negative. The book also took an opportunity to salute other legendary scientists and pioneers like Prof. B.E Tuch (Australia) and Prof. JL Tourane (France) who participated in the both the books.

The following book describes that why fetal tissue transplantation can be and is currently important in cell therapy. Stem cells with different potencies can be collected from different sources. Of all the stem cells, human embryonic stem cells (hESC’s) are normally regarded as the cells that can differentiate into all the three germ layers through the formation of embryoid bodies and when cultured under appropriate conditions such as feeder layer or growth factors they can remain in an undifferentiated state. However, ethics involving the isolation of human embryonic stem cells from human blastocyst stage and the formation of teratomas in some cases of animal models are some of the major limitations involved with the use of embryonic stem cells.

Other adult tissues like hematopoietic stem cells (HSC’s), Mesenchymal Stem cells (MSC’s) are much more limited in their capacity and potency compared to human embryonic stem cells (ESCs’s) as these are believed to multipotent stem cells compared to pluripotency of ESC’s.These various tissues like MSC’s, ESC’s, HSC’s and progenitor cell-like the Hematopoietic progenitor cells or HPC’s formed from the stem cells itself, highly proliferative endothelial cells or endothelial colony forming cells. Other new emerging therapeutic techniques like induced pluripotent stem cells are changing the field of stem cell therapeutics, however, the field of iPSC still needs some more time before it can be efficiently translated from the bench to bedside therapeutics.

The following book outlines the chapters pertaining to freshly collected properly screened and ethically collected fetal tissues from different organs for transplantation therapies and clinical research in treating various irreversible and chronic conditions after the patients volunteered for the studies. Different case studies like the use of fetal thymus transplants for arthritis, fetal brain transplant for treating neurodegenerative conditions, fetal pancreas for metabolic disorders like the diabetes are detailed with clinical observations, findings and results. Discussions are aplenty in the book often giving a hint why molecular studies are essential to understanding the process by which and how fetal tissue works in alleviating and curing symptoms which current medicine and surgery fail to do so. Different pre-clinical and molecular explanations have also been outlined stating that how the fetal tissue like the Mesenchymal stem cell can evade the host’s immune radar and possess an immune-modulatory mechanism rather than an immune suppressive one. The chapters written by one of the editors, Prof. Bhattacharya further outlines that how in some patients, even after 10 years the fetal tissues transplanted in the axilla region still survived and remained unscathed thereby opening another debate that whether stem cell therapy is cell mediated or cell cytokine based mediated. Also the author outlined that how the extracellular matrix played an important role in providing micro-architectural and microenvironmental support to the transplanted fetal tissue. .

The book has various chapters written by several eminent stem cell scientists and professors working with the issues and problems of fetal tissue transplantation and stem cell medicine. The Embryology of fetal tissue is discussed by eminent scientist and pioneer of the UK Blood Bank Prof. Peter Hollands. Further the in vitro and in vivo response of fetal issue to growth factors and its kinetics are explained by Harris Pratsinis et al. New and tougher concepts like how the fetus survives through accommodation and the fetomaternal trafficking during the course of pregnancy are explained in details by the tow editors of the book and J.L.Platt et al.

Topics like fetal tissue in kidney injury by Oren Pleniceanu et al., in utero transplantation of mesenchymal stem cells by Carolyn Troeger et al., and Hematopoietic stem cell transplantation for congenital disorders by Amar Nijagal et al., are explained in details in the book.Interesting chapters like the use of fetal tissue in musculoskeletal tissue engineering, tissue and cell therapy for treating various ailments like pituitary disorder, Parkinson’s disease, diabetes are described and works are shared by leading scientists in the field of regenerative medicine. The account of thymus transplantation conducted for the first time by Jean-Louis Touraine has also been included where the author has given her experience and the procedures and the findings of the Thymus transplantation and follow-up studies.

Several other chapters deals with the isolation of Mesenchymal stromal/stem cells from Wharton’s Jelly written by Dr. Weiss Lopez et al., Pluripotent stem cells from the embryo by De Miguel et al., in vitro models and in vivo models involving animal studies and fetal tissue’s potential role in healing the liver using fetal hepatocytes including hepatocytes for drug testing and bio-artificial livers using hepatocytes seeded on scaffolds has been explained in chapters written by eminent stem cell scientist Dr.’s Suchitra Holgersson, KJ Joshi, Olausson, Drs. Sakai Jiang, Hanada, Huang, Kojima, Teratani and Ochiya. An introduction of fetal porcine organs and their successful transplantation including achieving successful organogenesis and restoring functional organs are also covered in the book. Chapters pertaining to neural repair and regeneration for spinal cord and brain injuries are also described by Dr. Venkatachalam in one of the chapters. Futuristic topics like bio-banking where there will be an availability of fetal tissues, organs in a state of the art maintained facility are covered by Drs. Zeisberger, Weber and Hoerstrup et al., in the end, chapters of the book.Niranjan Bhattacharya, Phillip Stubblefield. Human Fetal Tissue Transplantation, Springer-Verlag London, 2013, Introduction, xxix.

Medical and bioethics another very important aspect of Fetal tissue transplantation has been aptly and discussed in detail by Prof. Sanjukta Bhattacharya, an eminent figure in the field of stem cell ethics and by Prof. Phillip Stubblefield where both the importance and the logic behind the use of fetal tissue in regenerative medicine and its immense potential in the field of cell therapeutics has been detailed. Questions like how ethical it is to collect a healthy fetus discarded or abandoned after the mother has given her consent to reject pregnancy and continue with medical termination of pregnancy are also discussed. What role does this otherwise so considered useless fetus post-termination of pregnancy can play in helping the healing of patients who are suffering from irreversible and end stage diseases and give them a ray of hope and a new life by utilizing its stem cells are also justified.

Conclusion
The book is aimed and meant for a wide range of professionals and audiences ranging from basic medical scientist to stem cell and biomedical scientists, medical professionals such as surgeons, clinicians and other super-specialized fields like gynecology, neurology, Pharmacology. The book is also cited in many articles including journals like Biomed Research International, Frontiers in Pharmacology.