ProGenaCell cellular Products

ProGenaCell manufactures and undergoes research drive from two primary cellular sources: umbilical cord blood and umbilical cord tissue. For some treatments, the research protocols may include the use of more than one type of cellular.

Umbilical Cord Blood-Derived cells (UCBSC)

For some conditions like spinal muscular atrophy, ataxia, and optic nerve conditions, ProGenaCell has developed treatments using umbilical cord blood (UCB) cells. Our UCB cellular injections consist of three subsets of cells: 1) hematopoietic cells, 2) endothelial progenitor cells, and 3) mesenchymal cells.

Hematopoietic cells and endothelial progenitor cells have been shown to develop into functional tissues. Mesenchymal cells are known to assist in the growth of chondrocytes – a type of cellular critical to tissue renewal, particularly cartilage – as well as liver cells, kidney cells and neurons. These cells also possess the ability to aid in the repair of a variety of vascular disorders within the brain, eye, and throughout the body including the heart, kidney, and pancreas. From our findings to date, it is believed that the benefits patients report following treatment arise from the cellular growth factors that are released by cells following administration.

Umbilical Cord-Derived Mesenchymal cells (UCMSC)

ProGenaCells protocols utilize UCMSC for treating conditions most amenable to cellular therapy. Our injections contain a higher percentage of mesenchymal cells than UCB cellular injections, closely resembling the composition of cells cultured from bone marrow. Current clinical guidelines recommend multiple sclerosis (MS) and spinal cord injury (SCI) patients receive these types of cellular injections. Previously published studies have demonstrated UCMSC produce important chemicals, known as growth factors, and have the ability to differentiate into desired cellular types, as well possessing the property of modulating the immune sy, reducing inflammation, scarring, and reducing cellular apoptosis.

ProGenaCell Neuronal Cellular Therapy

Multiple clinical applications have established that cellular therapy can be safe and effective in improving Quality of life and reducing difficulties of brain disorders like Parkinson's, Autism, Cerebral palsy, and Traumatic brain injury. Neuronal cells have shown to be most effective in homing to the nervous sy and repairing of damaged brain tissue after insult. ProGenaCell cells are harvested from fresh human cord blood for multiple reasons (see below)

ProGenaCell neuronal cells release a variety of trophic factors, growth factors, and cytokines known to enhance the reparative brain process. Direct replacement of cells with functional connections is less likely given the complexity of neural networks and the short time frame in which improvement is seen. Multiple mechanisms may work in some cases contributing to overall functional improvement. In the acute to subacute phase after stroke, the intravenous route might be best as a neuroprotective or anti-inflammatory strategy. At later time intervals, intrathecal routes might be preferable to better reach ischemic areas and deliver trophic factors. In a chronic stroke, direct intracerebral injection is more preferable for delivery cells to brain areas surrounding infarction capable of enhancing recovery. Our physicians implanted cells in subdural space overcoming technical difficulties in several cases.

ProGenaCell Integrative cellular Quality Control

ProGenaCell adheres to strict biological quality management and established the earliest and most complete quality standard sy for adult cells above and beyond USFDA, GTP, GMP.

• Laboratory standards for clinical-grade adult cellular processing.
• Safety and quality control sy for clinical-grade adult cells.
• Research and management sy for clinical-grade adult cells.
• Laboratory standards for clinical-grade adult cellular processing.
• Disease-specific translation protocols for clinical-grade adult cells.

Fresh Versus Frozen cells

Freezing cellular products during processing, can progressive injury during each of the three phases: 1) cooling 2) maintenance during cold, and 3) rewarming. In addition to metabolic imbalances, measurable changes also occur in the cellular and its organelle membrane lipid domains. These structural characteristics (transitions) result in a change in membrane fluidity from preferred liquid-crystalline state to less preferred solid gel state thus yielding a "leaky" membranous state. Moreover, a cascade of damaging cellular events generally occurs, including:

• Activation/leakage of lysosomal lipoprotein.
• Activation calcium-dependent phospholipases/release of free fatty acids.
• Activation of cellular death.
• Disruption of the cytoskeletal matrix.
• Generation of free radicals/oxidative stressors caused by freezing can result in forced cellular death or gene regulated cellular death.

"Cryopreservation: An emerging paradigm change."
— Baust JG1, Gao D, Baust JM. 2009.

The vast majority of cellular centers use frozen cells exceedingly more than fresh cells, because:

• Ease of transportation and storage (often up to three or four years) administration, patient treatment.
• Significant reduction in production costs because of the large number of cells that can be processed from the cord blood at one time, versus a single batch of custom cells made from fresh cord blood that can stay refrigerated for several days only, not months or years, and;
• Large quantity of frozen cells can be administered to multiple patients within the single setting (delivery time from laboratory to patient implantation is inconsequential) versus single treatment setting for a single patient (very limited four hour windrow delivery time from laboratory to patent implantation is crucial).

Cellular Delivery Route

Several routes of delivery are used to treat degenerative brain disorders; 1) intravenous delivery is quick and non-invasive, but cells get filtered through the lungs, multi-organ exposure and require large quantities of cells. 2) Intra-arterial delivery is more invasive than IV, can cause cellular clumping, but more targeted delivery to the brain, and uses a smaller quantity of cells compared to IV. 3) Intrathecal delivery is the most invasive, but provides the most direct delivery of cells to the brain, and uses the least quantity of cells. ProGenacell physicians 3) intrathecal delivery as its method of choice.

Cellular Clinical Historical Research, Clinical Trials and Medical Publications

Contrary to many modern day cellular therapy critics and pundits, cellular therapy has played a major role in treating most degenerative diseases since the 1930s. cellular Therapy is meant to treat chronic viral, degenerative, congenital, allergic, and some cancerous diseases from an entirely different approach than that of a more drug-oriented clinical environment.

Properly prepared cells are known to induce tissue-specific structural and functional regeneration in disorders related to the connective tissue, neurological, vascular, respiratory, and digestive and immune sys. The main reason for a delay in acceptance from American physicians is the failure of university teaching centers to instruct in this modality, aggressive pharmaceutical industry influence, and that nearly all medical literature about cellular therapy is written in German. A wealth of peer-reviewed basic science and clinical publications globally document the mechanism of action and efficacy of cellular therapy in a number of forms, regardless of language.

These two pathways to health are not mutually exclusive, nor considered competitive. Conventional standards of care tend to work better with emergent or acute problems e.g. trauma, rapid tissue failure, acute inflammation, and infection. Wherein cellular therapy is more oriented to chronic degenerative diseases, non-healing wounds, compromised immune sy, disturbed childhood development, premature aging, chronic allergies, and endocrine dysfunctions.

In the 1920's Russia ophthalmologist, Vladimir Filatov initiated the application of fetal cellular extract therapies for non-specific rejuvenation of chronically ill patients. His earliest claimed successes were reversing retinitis pigmentosa and macular degeneration.

In the 1930s, surgeon Paul Niehans, became increasingly interested in endocrinology, while Chief of Staff at a renowned Swiss hospital. Specifically studying the work of colleagues experimenting with implantation of animal glands into patients whose organs were not functioning properly.

In 1954, a medical conference in Karlsruhe, Germany had over 5,000 practicing cellular therapy physicians attend the conference. It is a little known fact that over 2,000 medical publications have been written on cellular therapy since 1930, primarily in German or Russian.

n 1967, the only known English publication on cellular therapy by "Schmid F, Stein J. cellular-Research and cellular Therapie (Ott Publishers, Thun, Switzerland, 1967)" which also included papers by researchers from Germany, Austria, Greece, and Spain, succinctly presented the scientific and medical basis for cellular therapy.

In 1975, "Literaturverzeichnes der Internationalen Forshungsgesellschaft fur Zelltherapie" a compendium of the most significant cellular therapy advances to date, was published in German to the receptive reading audience.

From 1976 through 1990 dozens of biannual cellular Transplantation Symposiums were held throughout the former Soviet Union proffering cogent evidence of the safety and efficacy of cellular therapy.

In 1992, American researchers reported early success with fetus-to-fetus cellular therapy for treating a severe genetic abnormality. Ismail Zanjani of the University of Nevada reported that transplanted human fetal tissue had "taken hold" in an infant born a year before, with many of the child's blood-making cells apparently descendants of transplanted cellular tissue. The parents had previously lost two children to this syndrome. The case opened a controversy over using human fetal tissue in experimental therapy. The U.S. government position in the early 1990s was that such use might encourage abortions and illegal trafficking of human fetuses.

In the 1980s, western medicine began to "legitimize" cellular therapy, beginning with the work of Dr. Michael Osband (NEJM, 1981): Ten of the 17 children treated for Histiocytosis X experienced complete remission after receiving intramuscular injections of thymus extract from five-day-old calves. This was the first reported use of a crude form of non-human live cellular therapy under controlled conditions conducted within the U.S..

In 1983, the American Paralysis Association convention was told that cells taken from human aborted fetuses and injected into animals provided evidence of useful repair of spinal cord accidents and degenerative diseases.

In 1988, The LA Times reported that Dr. Kevin Lafferty, of the University of Colorado, saw "good results" in six of 17 diabetic patients treated with "implanted cells" from fetal pancreases. The Times also reported that about 200 patients worldwide had received fetal liver cells, primarily to restore bone marrow loss because of cancer therapy. And that Dr. Robert Gale of UCLA, had implanted fetal liver cells into six radiation victims of the (then) Soviet Union's 1986 Chernobyl nuclear disaster (an ironic case in which American researchers utilized a form of therapy the American medical establishment considered unproven at best, and quackery at worst, to help save lives in a foreign country).

In 1995 and 1996 other examples of advances in cellular therapy were exhibited when treating Myocardial Infarctions and other heart diseases; based in large part by the experimental works of Chiu RC (1995), Li RK (1996), and Menasche P (1996), with each preceded by the well-documented clinical experiences of both German practitioners of cellular therapy and Soviet cellular transplantologists decades earlier.

Below are just a few of the over 2,000 medical journals referenced above.

Menasche P, Hagege A, Scorsin M, et al. Autologous skeletal myoblast transplantation for cardiac insufficiency. First clinical case. Arch Mal Coeur Vaiss 2001;94:180-2.

Strauer BE, Brehm M, Zeus T, et al. Intracoronary, human autologous cellular transplantation for myocardial regeneration following myocardial infarction. Dtsch Med Wochenschr 2001: 126:932-8.

Strauer BE, Brehm M, Zeus T, et al. Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cellular transplantation. Circulation 2002; 106:1913-6.

Suzuki K, Murtuza B, Heslop L, et al. Single fibers of skeletal muscle as a novel graft for cellular transplantation to the heart. J Thorac Cardiovasc Surg 2002;123:984- 92.

Pouzet B, Ghostine S, Vilquin JT, et al. Is skeletal myoblast transplantation clinically relevant in the era of angiotensin-converting enzyme inhibitors, Circulation 2001;104 (Suppl 1):1223-8.

Jain M, DerSimonian H, Brenner DA, et al. cellular therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation 2001;103:1920-7.

Shake JG, Gruber PJ, Baumgartner WA, et al. Mesenchymal cellular implantation in a swine myocardial infarct model: engraftment and functional effect. Ann Thorac Surg 2002;73:1919-25.Li RK, Jia ZQ, Weisel RD, Marante F, Mickle DA. Smooth muscle cellular transplantation into myocardial scar tissue improves heart function. J Mol cellular Cardiol 1999;31:513-22.

Min YI, Yang Y, Converso KL, et al. Transplantation of embryonic cells improves cardiac function in postinfarcted rats. J Appl Physiol 2002;92:288-96 10- Malouf NN, Coleman WB, Grisham JW, et al. Adult-derived cells from the liver become myocytes in the heart in vivo. Am J Pathol 2001;158:1929-35 11- Matsushita T, Oyamada M, Kurata H, et al. Formation of cellular junctions between grafted and host cardiomyocytes at the border zone of rat myocardial infarction. Circulation 1999;19 (Suppl II):262-8.

Ruhparwar A, Tebbeenjohans J, Niehaus M, et al. Transplanted fetal cardiomyocytes as cardiac pacemaker. Eur J Cardiothorac Surg 2002;21:853-7.

Scorsin M, Hagege A, Vilquin JT, et al. Comparison of the effects of fetal cardiomyocytes and skeletal myoblasts transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg 2000;119:1169-75.

Sakai T, Li RK, Weisel RD, et al. Fetal cellular transplantation: a comparison of three cellular types. J Thorac Cardiovasc Surg 1999;118:714-24.

Hutcheson KA, Atkins BZ, Hueman MT, et al. Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts cellular Transplant 2000;9:359-68.

Li RK, Mickle DA, Weisel RD, Rao V, Jia ZQ. Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury. Ann Thorac Surg 2001;72:1957-63.

Roell W, Lu ZJ, Bloch W, et al. cellular cardiomyoplasty improves survival after myocardial injury. Circulation 2002;105: 2435-41.

Muller-Ehmsen J, Peterson KL, Kedes L, et al. Rebuilding a damaged heart: long-term survival of transplanted neonatal rat cardiomyocytes after myocardial infarction and effect on cardiac function. Circulation 2002;105:1720-26.

Saito T, Kuang JQ, Bittira B, Al-Khaldi A, Chiu RC. Xenotransplant cardiac chimera: immunotolerance of adult cells. Ann Thorac Surg 2002;74:19-24 cells and myocardial regeneration.

Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD. Human mesenchymal cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 2002;105:93-8.

Etzion S, Battler A, Barbash IM, et al. Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. J Mol cellular Cardiol 2001;33:1321-30.

Kim EJ, Li RK, Weizel RD, et al. Angiogenesis by endothelial cellular transplantation. J Thorac Cardiovasc Surg 2001;122:963-71.

Dornbusch S. The effect of placenta on experimental cholesterinsclerosis. In Schmid F, Stein J. cellular-research and cellular therapy (Ott Publishers. Thun, Switzerland, 1967), 134-40.

Cunningham FG, MacDonald PC, Leveno KJ, Gant NF, Gilstrap LC. Williams Obstetrics. 19th ed (Appleton & Lange, 1993).

Schmid F, Stein J. cellular-research and cellular therapie (Ott Publishers, Thun, Switzerland, 1967).

Schmid F, Stein J. Zellforschung und Zelltherapie (Verlag H. Huber, Bern, Stuttgart, 1963).

Oetzmann HJ. cellular therapy for diseases of organs. In Schmid F, Stein J, cellular-research and cellular therapie (Ott Publishers. Thun, Switzerland, 1967), 149-85.

Schmid F. Zelltherapie-Grundlagen- Klinik-Praxis (Ott-Verlag, Thun, Switzerland, 1981).

Schmid F. cellular therapy, a New Dimension of Medicine (Ott Publishers, Thun, Switzerland, 1983).

Hendricks PJ, Martens A, Hagenbeek A, et al. Homing of fluorescently labaled murine hematopoietic cells. Exp Hematol 1996; 24:129-40.

Zanjani E, Ascensao J, Tavassoli M. Liver-derived hematopoietic cells selectively and preferentially home to the fetal bone marrow. Blood 1993;81:399- 404.

Hardy C. The homing of hematopoietic cells to the bone marrow. Am J Med Sci 1995; 309:260-6 33- Gilbert SF. Developmental Biology, 4th ed (Sinauer Associates, Sunderland MA, 1994).

Lenmark A, Freedman ZR, Hofmann C. Islet-cellular-surface antibodies in juvenile diabetes mellitus, N Eng J Med 1978;299: 375-80.

Kondrat'ev YaYu, Sadovnikova NV, Liozner AL, Fedotov VP. Antibodies to the surface of pancreatic islet cells: immunoenzymatic determination with rat target cells. Problemi endokrinologii 1986;32:39-43.

Hopf U, Meyer zum Buschenfelde KH, Freudenberg J. Liver-specific antigens of different species. Clin Exp Immunol 1974; 16:117-24.

Lodish H, Baltimore D, Berk A, Zipursky SL, Matsudaira P, Darnell J. Molecular cellular Biology, 3rd ed (Scientific American Books, New York, 1995).

cellular Transplantation Clinical Research USSR / Russian Federation (1990 through 1997)

Regeneration - Rejuvenation - Revitalization

Research Center of Pediatrics (RAMS) (Academician Studenikin) Division of Nephrology: Genetic diseases, Chronic nephritis

• Division of Hematology: Aplastic anemia, M. Gaucher.
• Division of Gastroenterology: Chronic hepatitis, Liver cirrhosis.
• Division of Neuropsychiatry: Cerebral palsy, birth-related brain damage.
• Division of Cardiology: Cardiomyopathy.
• Pediatric Hospital of First Moscow Medical School (Academician Baranov):
  • Collagen diseases.
• Research Center of Endocrinology (RAMS) (Academician Dedov):
  • Nanism.
  • Congenital hypothyroidism.
• First Republican Pediatric Hospital of MHRF (Dr. Burkov):
  • Transplantation of human fetal testis.
• Rehab. Center of First Moscow Medical School (Prof. Grinio):
  • Muscular Dystrophy.
• Medical Center of the President of Russian Federation (Dr. Mironov):
  • Down syndrome, pediatric genetic diseases.
  • Immune diseases, including AIDS.
  • Cellular neuro-transplantation via intrathecal route for untreatable neurological diseases.
• Research Center of Transplantology and Artificial Organs (MHRF) (Academician Shumakov):
  • Complications of type insulin Dependent Diabetes Mellitus Type 1.
  • Male infertility.
  • Hypo-endocrinopathies.
• Research Center of Emergency Medicine (RAMS) Division of Neurosurgery (Dr. Lebedev):
  • Neurotransplantation for Parkinson's disease, for aphasia after severe brain damage.
  • Injuries, for status post-cerebrovascular accident.
• Moscow Burn Center (Dr. Smirnov):
  • Non-surgical treatment of deep thermal burns (requiring skin grafting).
• Research Center of Medical Radiology (RAMS) (Academician Tsyb)
  • Post-therapeutic radiation damage of soft tissues.
• Research Center of Biophysics (MHRF) (Academician Il'yin):
  • Treatment of accidental radiation injuries.
• Research Center of Obstetrics, Gynecology, Perinatology (RAMS) (Academician Kulakov)
  • Early menopause of various etiologies.
  • Endometriosis.
  • Intrauterine brain damage (early treatment).
  • Infertility, female and male.
  • Research Center of Human Reproduction (MHRF) (Dr. Vasiliev):
    • Male infertility and impotence.
  • Central Institute of Traumatology and Orthopedics (RAMS) (Dr. Shaposhnikov):
    • Surgery of severe inborn deformities.
  • Helmholtz Research Center of Ophthalmology (RAMS) (Dr. Brovkina)
    • Myopathy of eye muscles.
    • Perforation of eye after therapeutic irradiation.
  • Fedorov Eye Research Institute (Dr. Fedorov):
    • Retinitis pigmentosa.
    • Diabetic retinopathy.
  • Research Institute of Medical Technology (MHRF) (Dr. Davydov)
    • Biodegradable biopolymers saturated with cellular transplants for reconstructive surgery and artificial organs.
    • First Stomatological Institute.