- Henry E. Young PhD received a BS in Biology in 1974 from Ohio State University, Columbus, OHedit
- Dr Abbott S. Gaunt, 1972-1974, Dr. Claudia F. Bailey, 1974-1977, Dr. Perry M. Johnston, 1974-1977, Dr. Bernell K. Dalley, 1977-1983, Dr. Roger R. Markwald, 1977-1983, Dr. Arnold I. Caplan, 1983-1987, Dr. James Kimura, 1987-1988edit
Naïve adult endogenous stem cell transplants have been used as a substitute for embryonic stem cells and/or induced pluripotent stem cells for treating individuals with autoimmune, cardiovascular, neurological, orthopedic, pulmonary,... more
Naïve adult endogenous stem cell transplants have been used as a substitute for embryonic stem cells and/or induced pluripotent stem cells for treating individuals with autoimmune, cardiovascular, neurological, orthopedic, pulmonary, renal and systemic chronic diseases and traumatic injuries. This is primarily due to the absence of moral and ethical issues, absence of teratoma formation when transplanting stem cells in the naïve state, readily available populations of stem cells and ease of stem cell isolation for transplant. While a majority of the ongoing clinical trials utilize autologous naive adult endogenous stem cells for treating the individual with their own stem cells, other trials have utilized similar types of allogenic stem cells from donors for the treatment of chronic diseases. For allogeneic naïve endogenous adult stem cells to be utilized for transplant, the donor stem cells should be screened to prevent the
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Previous studies have reported the presence of endogenous undifferentiated totipotent stem cells within the organs and tissues of various animal species, including the spleen. Since one major function of the spleen is to filter out... more
Previous studies have reported the presence of endogenous undifferentiated totipotent stem cells within the organs and tissues of various animal species, including the spleen. Since one major function of the spleen is to filter out damaged red blood cells, we wanted to ascertain whether totipotent stem cells existed as a potentially transient circulating population solely within the vasculature and sinusoids of the spleen or whether they existed as an endogenous resident population of primitive stem cells throughout the tissues of the spleen, and potentially involved in the repair of the spleen. The spleens from two separate mammalian species were examined, i.e., adult pigs and adult rats. Adult pigs were euthanized following the guidelines of Fort Valley State University’s IACUC. Adult rats were euthanized following the guidelines of Mercer University School of Medicine’s IACUC. The spleens were harvested, fixed, frozen, cryosectioned, and stained with an antibody diagnostic for the endogenous totipotent stem cells, i.e., Carcinoembryonic Antigen-Cell Adhesion Molecule-1 (CEA-CAM-1). CEA-CAM-1 positive stem cells were located within the capsule of the spleen, along the splenic trabeculae, within the red pulp, within the white pulp, along the central arteries and surrounding the penicillar arteries of the spleen in both the adult pig and in the adult rat. These results suggested that the totipotent stem cells are a resident population of stem cells within the splenic tissues. Studies are ongoing to address their functional significance in repair of the spleen.
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Early clinical studies with telomerase-positive stem cells demonstrated no response when these stem cells were mixed with lidocaine prior to clinical treatments in multiple individuals. Their stem cells demonstrated a positive response... more
Early clinical studies with telomerase-positive stem cells demonstrated no response when these stem cells were mixed with lidocaine prior to clinical treatments in multiple individuals. Their stem cells demonstrated a positive response when mixed with normal sterile saline utilizing alternative routes of implantation. We hypothesized that lidocaine killed the stem cells before injection and that dead stem cells would give no response. We tested five local anesthetics, e.g., bupivacaine, lidocaine, marcaine, novocaine and procaine, with sterile saline in a series of blinded experiments to determine their ability to affect the viability of telomerase-positive stem cells. A mixture of TSCs, PSCs and MesoSCs were utilized from five individuals, three males and two females. Trypan blue was used to distinguish live versus dead PSCs and MesoSCs. The number of dead cells divided by total number of cells and multiplied by 100 was used for each test solution to determine their respective % kill ratio. Sample size was n=180 for each test solution. Lidocaine demonstrated a 100% kill ratio; novocaine and procaine demonstrated a 50% kill ratio and marcaine, bupivacaine and sterile saline demonstrated a 0% kill ratio. The
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The objectives of the work, based on previous characterization studies, pre-clinical animal models of induced diseases, e.g., Parkinson disease, cardiovascular disease, pulmonary disease, and type-I diabetes mellitus, and early clinical... more
The objectives of the work, based on previous characterization studies, pre-clinical animal models of induced diseases, e.g., Parkinson disease, cardiovascular disease, pulmonary disease, and type-I diabetes mellitus, and early clinical human studies of Parkinson disease, cardiovascular disease, and pulmonary diseases, were to established a set of criteria that needed to be followed for using telomerase-positive stem cells in future human clinical trials. From this set of criteria, informed consent guidelines were established to optimize the safety and efficacy of using endogenous adult-derived telomerase-positive stem cells to restore organ function by either repair and/or regeneration of cells and tissues resulting from tissue damage and/or loss. Inclusion criteria were any male or female, 18 to 120 years of age, with preferably no serious comorbidities. Exclusion criteria were use of alcohol, tobacco products, vaping, recreational drugs, lidocaine, and/or chemotherapeutic drugs. We also cautioned use of caffeine and corticosteroids, as well as limiting moderate to strenuous physical activity within a two
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Endogenous adult-derived Totipotent Stem Cells (TSCs) and tissue-resident exosomes are major players in the field of regenerative medicine. TSCs provide the undifferentiated building blocks for tissue repair, while exosomes provide the... more
Endogenous adult-derived Totipotent Stem Cells (TSCs) and tissue-resident exosomes are major players in the field of regenerative medicine. TSCs provide the undifferentiated building blocks for tissue repair, while exosomes provide the directions on how these building blocks should be used to accomplish this feat, i.e., restoration of fully functional tissue. Both TSCs and exosomes have been extensively characterized with respect to composition and function. While they have similar characteristics in four categories, they differ with respect to each other in a myriad of other categories. The following is criteria used by this lab to distinguish telomerase-positive totipotent stem cells from bioactive factor-containing exosomes.
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Research Interests: Tissue Engineering, Regeneration, Skeletal muscle biology, Induced Pluripotent Stem Cells (I Psc), Stem Cell, and 24 moreTranscription Factors, Neurodegenerative Diseases, Telomerase, Higher Order Thinking, Cell Differentiation, Humans, Diabetes mellitus, Animals, Cell Death, Connective tissue, Single Cell, Cattle, Rats, Myocardial Infarction, Model System, Urodela, Life Span, DNA binding proteins, Bone and Bones, Cell Sorting, Biochemistry and cell biology, Tissue Specificity, Extremities, and Hematopoietic Stem Cell Transplantation
Chronic kidney disease is an increasing public health issue. Prevalence has been estimated to be 8-16% worldwide. Complications include increased mortality including cardiovascular mortality, progression of kidney disease, acute kidney... more
Chronic kidney disease is an increasing public health issue. Prevalence has been estimated to be 8-16% worldwide. Complications include increased mortality including cardiovascular mortality, progression of kidney disease, acute kidney injury, cognitive decline, anemia, disorders of mineral and bone, and fractures. Two types healing cells, pluripotent stem cells and totipotent stem cells, have been located, isolated and characterized from skeletal muscle, adipose tissue, bone marrow, dermis, and blood of adult animals, including humans. The current study was undertaken to determine whether these two populations of healing cells were present in the kidney of the adult rat. Adult rats were euthanized following the guidelines of Mercer University's IACUC. The kidneys were harvested, fixed, cryosectioned and stained with two antibodies diagnostic for these healing cells, i.e., stage-specific embryonic antigen-4 (SSEA-4) for pluripotent stem cells and carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) for totipotent stem cells. Cells staining for SSEA-4 were located amongst the tubules in the medulla of the kidney, whereas cells staining for CEA-CAM-1 were located among the glomeruli in the cortex of the kidney and among the tubules in the medulla of the kidney. This is the first report of native populations of both pluripotent and totipotent healing cells in the adult rat kidney. Studies are ongoing to address their functional significance during normal kidney maintenance and repair.
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Stage-specific antigen-4 (SSEA-4) positive cells and carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) positive cells, indicative of pluripotent stem cells and totipotent stem cells, respectively, have been isolated and... more
Stage-specific antigen-4 (SSEA-4) positive cells and carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) positive cells, indicative of pluripotent stem cells and totipotent stem cells, respectively, have been isolated and characterized from the skeletal muscle and blood of adult animals, including humans. The current study was undertaken to determine their location in the dermis and underlying connective tissues of the adult pig. Adult pigs were euthanized following the guidelines of Fort Valley State University's IACUC. The skin (epidermis through hypodermis) was harvested, fixed, cryosectioned, and stained with the two antibodies: SSEA-4 and CEA-CAM-1. SSEA-4 positive cells were located preferentially in the reticular dermis of the skin and to some extent in the underlying hypodermis. In contrast, CEA-CAM-1 positive stem cells were preferentially located within the hypodermis of the pig skin within the loose fibrous connective tissues surrounding adipose tissue. CEA-CAM-1 positive cells were also located, to a lesser extent, in the dermis as well. These results demonstrate the presence of native populations of pluripotent stem cells and totipotent stem cells within the dermis, hypodermis, and adipose tissue of adult pig skin. Studies are ongoing to address the functional significance of these cells in normal injury and repair.
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This study was designed to determine if trauma causes the release of adult-derived blastomere-like stem cells (BLSCs) from skeletal muscle into the circulating blood of adult pigs. Experimental procedures followed the guidelines of Fort... more
This study was designed to determine if trauma causes the release of adult-derived blastomere-like stem cells (BLSCs) from skeletal muscle into the circulating blood of adult pigs. Experimental procedures followed the guidelines of Fort Valley State University's Institutional Animal Care and Utilization Committee. Pigs were traumatized by splenectomy followed by pancreatectomy. Blood samples and skeletal muscle biopsies were taken before and after trauma. Adult-derived BLSCs were isolated from skeletal muscle and blood samples following established procedures. Nontraumatized skeletal muscle contained approximately 277 million BLSCs per gram of muscle. After trauma, skeletal muscle contained approximately 2 million BLSCs per gram of muscle. Blood taken before trauma contained approximately 22 million BLSCs per milliliter, whereas approximately 512 million BLSCs per milliliter were present within the blood after trauma. Blood values were statistically significant with a P < 0.0...
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Primitive healing cells, i.e., pluripotent stem cells and totipotent stem cells, have been isolated from the skeletal muscle and blood of adult mammals, including humans. The current study was undertaken to determine the location of these... more
Primitive healing cells, i.e., pluripotent stem cells and totipotent stem cells, have been isolated from the skeletal muscle and blood of adult mammals, including humans. The current study was undertaken to determine the location of these cells with respect to normal and regenerating lung parenchyma of the adult rat. Adult rats were euthanized following the guidelines of Mercer University's IACUC. The lungs were fixed, cryosectioned and stained with two antibodies diagnostic for primitive adult stem cells, i.e. SSEA-4 for pluripotent stem cells and CEA-CAM-1 for totipotent stem cells. In non-injured lung tissue SSEA-4 positive stem cells were located in areas of the smooth muscle within the parenchyma and bronchioles, whereas CEA-CAM-1 positive stem cells were located within the smooth muscle and visceral pleura. Both primitive stem cells were present in injured lung parenchyma undergoing repair. IRB-approved clinical studies are ongoing to address their functional significance in human clinical pulmonary injury and repair.
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Pulmonary disease is a source of serous morbidity and mortality. Cell treatments offer hope for rejuvenation and repair of damaged lungs. The possibility of using maintenance cells and/or healing cells to repair damaged lungs has been... more
Pulmonary disease is a source of serous morbidity and mortality. Cell treatments offer hope for rejuvenation and repair of damaged lungs. The possibility of using maintenance cells and/or healing cells to repair damaged lungs has been studied for nearly two decades. This paper reviews pertinent research investigating the different models and approaches that have been studied concerning the use of donor-derived cells to increase alveolar stem cells in damaged lungs.
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Primitive healing cells, i.e., pluripotent stem cells and totipotent stem cells, have been isolated from the skeletal muscle and blood of adult mammals, including humans. The current study was undertaken to determine the location of these... more
Primitive healing cells, i.e., pluripotent stem cells and totipotent stem cells, have been isolated from the skeletal muscle and blood of adult mammals, including humans. The current study was undertaken to determine the location of these cells with respect to normal and regenerating lung parenchyma of the adult rat. Adult rats were euthanized following the guidelines of Mercer University's IACUC. The lungs were fixed, cryosectioned and stained with two antibodies diagnostic for primitive adult stem cells, i.e. SSEA-4 for pluripotent stem cells and CEA-CAM-1 for totipotent stem cells. In non-injured lung tissue SSEA-4 positive stem cells were located in areas of the smooth muscle within the parenchyma and bronchioles, whereas CEA-CAM-1 positive stem cells were located within the smooth muscle and visceral pleura. Both primitive stem cells were present in injured lung parenchyma undergoing repair. IRB-approved clinical studies are ongoing to address their functional significance in human clinical pulmonary injury and repair.
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Pulmonary disease is a source of serous morbidity and mortality. Cell treatments offer hope for rejuvenation and repair of damaged lungs. The possibility of using maintenance cells and/or healing cells to repair damaged lungs has been... more
Pulmonary disease is a source of serous morbidity and mortality. Cell treatments offer hope for rejuvenation and repair of damaged lungs. The possibility of using maintenance cells and/or healing cells to repair damaged lungs has been studied for nearly two decades. This paper reviews pertinent research investigating the different models and approaches that have been studied concerning the use of donor-derived cells to increase alveolar stem cells in damaged lungs.
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Recent reports demonstrated the presence of primitive endogenous stem cells circulating within adult cat, dog, sheep, goat, pig, cow, and horse peripheral blood. The current study was undertaken to determine whether similar primitive stem... more
Recent reports demonstrated the presence of primitive endogenous stem cells circulating within adult cat, dog, sheep, goat, pig, cow, and horse peripheral blood. The current study was undertaken to determine whether similar primitive stem cells could be isolated from the peripheral blood of adult humans. Adult humans had their blood withdrawn following the guidelines of Mercer University School of Medicine and the Medical Center of Central Georgia Institutional Review Boards. The blood was obtained by venipuncture and processed to obtain primitive stem cells. Cells were identified and counted using 0.4% Trypan blue inclusion/exclusion analysis and stained with carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) antibody. Totipotent stem cells are both trypan blue and CEA-CAM-1 positive and <2.0 microns in size; transitional-totipotent/pluripotent stem cells are both trypan blue and CEA-CAM-1 positive & negative and >2.0 to <6.0 microns in size; and pluripotent stem cells are both trypan blue and CEA-CAM-1 negative and 6-8 microns in size. The results show that TSCs, Tr-TSC/PSCs, and PSCs are circulating within the peripheral blood of adult humans. Studies are ongoing to address their functional significance during maintenance and healing.
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Stout et al. [1] reported the presence of primitive endogenous stem cells circulating within adult porcine peripheral blood. The current study was undertaken to determine whether similar primitive stem cells could be isolated from the... more
Stout et al. [1] reported the presence of primitive endogenous stem cells circulating within adult porcine peripheral blood. The current study was undertaken to determine whether similar primitive stem cells could be isolated from the peripheral blood of adult felines, canines, ovines, caprines, bovines, and equines. Adult cats, dogs, sheep, goats, cows and horses had their blood withdrawn following the guidelines of Fort Valley State University's IACUC. The blood was obtained by venipuncture and processed to obtain primitive stem cells. Cells were counted using 0.4% Trypan blue inclusion/exclusion analysis and stained with carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) antibody. Totipotent stem cells are both trypan blue and CEA-CAM-1 positive and < 2.0 microns in size; transitional-totipotent/pluripotent stem cells are both trypan blue and CEA-CAM-1 positive & negative and >2.0 to <6.0 microns in size; and pluripotent stem cells are both trypan blue and CEA-CAM-1 negative and 6-8 microns in size. The results show that TSCs, Tr-TSC/PSCs, and PSCs are circulating within the peripheral blood of all species examined. Studies are ongoing to address their functional significance during maintenance and healing.
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Development of a multicellular organism is accomplished through a series of events that are preprogrammed in the genome. These events encompass cellular proliferation, lineage commitment, lineage progression, lineage expression, cellular... more
Development of a multicellular organism is accomplished through a series of events that are preprogrammed in the genome. These events encompass cellular proliferation, lineage commitment, lineage progression, lineage expression, cellular inhibition, and regulated apoptosis. The sequential progression of cells through these events results in the formation of the differentiated cells, tissues, and organs that constitute an individual [1]. Although most cells progress through this sequence during development, a few cells leave the developmental continuum to become reserve precursor cells. The reserve precursor cells are involved in the continual maintenance and healing of the tissues and organs throughout the life span of the individual. Until recently it was generally assumed that the precursor cells in postnatal individuals were limited to lineage-committed unipotent progenitor cells specific for various cells, i.e., neuroblasts for neurons, myoblasts for muscle, hepatoblasts for hepatocytes. However, recent studies [1-3] demonstrated the presence of two categories of precursor cells that reside within the organs and tissues of postnatal animals. These two categories of precursor cells are maintenance cells and healing cells. These reserve precursor cells provide for the continual maintenance and repair of the organism after birth.
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Endogenous naturally-occurring totipotent stem cells and pluripotent stem cells have been isolated from the skeletal muscle of adult mammals, including humans. This study was undertaken to determine their particular location within adult... more
Endogenous naturally-occurring totipotent stem cells and pluripotent stem cells have been isolated from the skeletal muscle of adult mammals, including humans. This study was undertaken to determine their particular location within adult rat skeletal muscle and to verify the identity of the stained cells. Adult rats were euthanized following the guidelines of Mercer University's IACUC. Skeletal muscle was harvested and processed for immunocytochemistry. Cells were stained with carcinoembryonic antigen-cell adhesion molecule-1 (CEA-CAM-1) and stage-specific embryonic antigen-4 (SSEA-4). Positive and negative staining controls were run to verify the validity of the immunostaining. CEA-CAM-1+ cells were located preferentially within vascular connective tissues, whereas SSEA-4+ cells were located preferentially within neuronal connective tissues. CEA-CAM-1+ stem cells and SSEA-4+ cells were isolated from adult rat skeletal muscle, segregated, cloned from single cells, and their unique morphologies, differentiation potentials, and attributes in culture were subsequently characterized. Four populations of stem cells were identified that share the CEA-CAM-1 and/or SSEA-4 epitopes. Totipotent stem cells and transitional-totipotent stem cell/pluripotent stem cells share the CEA-CAM-1 epitope, whereas the transitional-totipotent stem cell/pluripotent stem cells, pluripotent stem cells, and transitional-pluripotent stem cell/germ layer lineage stem cells share the SSEA-4 epitope. This report describes native populations of endogenous naturally-occurring totipotent stem cells and pluripotent stem cells in adult rat skeletal muscle. Studies are ongoing to address their functional significance during normal tissue maintenance and repair of body organs.
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This study was designed to test the hypothesis that decellularized pancreatic matrices seeded with adult-derived endogenous stem cells and donor islets provide an optimal environment for islets to secrete insulin in response to a glucose... more
This study was designed to test the hypothesis that decellularized pancreatic matrices seeded with adult-derived endogenous stem cells and donor islets provide an optimal environment for islets to secrete insulin in response to a glucose challenge. Adult animals were euthanized following the guidelines of Fort Valley State University-IACUC and Mercer University-IACUC. Adult porcine pancreases were decellularized using a mixture of detergents. Adult rat pancreatic islets were obtained by lipase digestion followed by Ficoll gradient sedimentation. Control cultures consisted of decellularized matrices, clonal populations of naïve adult totipotent and pluripotent stem cell populations, and rat islets, all cultured individually. Experimental groups consisted of islets co-cultured with clonal populations of pluripotent stem cells and totipotent stem cells seeded on decellularized matrices. Control and experimental cultures were challenged with the insulin secretagogue glucose. The control and culture media were removed and stored at-20oC until assayed using a RIA specific for rat insulin. The culture media, containing bovine insulin, were assayed using a RIA specific for rat insulin. No detectable levels of insulin (bovine, rat, human, or porcine) were noted in media only, the stem cell populations or the decellularized matrices, respectively. Native pancreatic islets secreted nanogram quantities of insulin per nanogram of DNA. Pancreatic islets co-cultured with naïve stem cells and matrices demonstrated increased insulin secretion in the range of milligram quantities of insulin per nanogram of DNA, i.e., a 250-fold increase in insulin secretion in response compared to pancreatic islets alone. These studies suggest that native islets in combination with decellularized matrices and adult-derived pluripotent and totipotent stem cells could provide more tissue for pancreatic islet transplants than donor islets alone.
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Regeneration in the adult salamander, Ambystoma annulatum, parallels that of the adult newt (I ten & Bryant, 1973). However, a number of unique features become apparent upon examination ofanomalies of adult regenerates. Tworegenerates... more
Regeneration in the adult salamander, Ambystoma annulatum, parallels that of the adult newt (I ten & Bryant, 1973). However, a number of unique features become apparent upon examination ofanomalies of adult regenerates. Tworegenerates whichdisplayed gross ab- normalities revealed, upon histological examination, unique features which give insight into a possible pattern of digit formation in this species of adult salamander. Normal regenerates show 4 or 5 digits radiating distal to the same respective number of bones (distal carpals) present in the distal row of wrist bones. The first anomaly showed only twolarge, fused distal carpals and twolateral digits. The second anomaly contained three bones in thedistal row of wrist bones and three digits. From the above observations, one might postulate that since the number of digits that willeventually occur corresponds to the number of wrist bones foundin the distal row, then the presence of a proper number of wrist bones in the distal row...
Regeneration was studies in the Ambystoma annulatum by amputation of the right forearm of twenty-four adults, over a twelve month period. At termination of the experiment the limbs were reamputated 1-2 mm proximal to the original... more
Regeneration was studies in the Ambystoma annulatum by amputation of the right forearm of twenty-four adults, over a twelve month period. At termination of the experiment the limbs were reamputated 1-2 mm proximal to the original amputation site. The regenerated portions were staged, examined at the gross morphological level, and prepared for histological examination. Gross examination revealed a thickened…