Stem Cell in Disease

  • Spinal Cord Injury

    Spinal cord is a bundle of nerves enclosed in vertebral column (back bone) that runs down the middle of your back. It transmits signals back and forth between your different parts of body and your brain. A spinal cord injury is the damage to any part of the spinal cord due to motor vehicle accidents, falls, violence, sports injuries, industry-related injuries. etc. often causing long lasting or sometimes permanent changes in the strength, sensation and other body functions below the site of the injury.

    Spinal cord injuries of any kind may cause any, some or all of the following signs and symptoms:

    • Loss of movement

    • Loss of sensation, including the ability to feel heat, cold and touch

    • Loss of bowel or bladder control

    • Exaggerated reflex activities or spasms

    • Changes in sexual function, sexual sensitivity and fertility

    • Pain or an intense stinging sensation caused by damage to the nerve fibers in your spinal cord

    • Difficulty breathing, coughing or clearing secretions from your lungs

    Role of Stem Cells in Spinal Cord Injury

    After spinal cord injury endogenous regenerative events set on, signifying body’s attempt to repair injury. Schwann cells, the myelinating and regeneration-promoting cells move from spinal roots into the damaged tissue and myelinate spinal cord axons [1, 2]. There is also an increase in the proliferation of local adult stem cells and progenitor cells [3, 4]. Mesenchymal stem cells from bone marrow may have therapeutic promise for SCI [5,6]. There are reports that BM MSCs transplantation therapy in patients with Spinal Cord Injury. In one report patients showed motor improvement of the upper extremities [7]. Currently, there have been a numerous clinical and experimental studies showing positive results in terms of functional improvement with stem cell treatment in SCI [8].

    1. Requirements for Schwann cell migration within CNS environments: a viewpoint. Franklin RJ, Blakemore WF Int J Dev Neurosci. 1993.

    2. Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat thoracic spinal cord. Takami T, Oudega M, Bates ML, Wood PM, Kleitman N, Bunge MB J Neurosci. 2002 Aug 1; 22(15):6670-81.

    3. In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord. Martens DJ, Seaberg RM, van der Kooy D Eur J Neurosci. 2002 Sep; 16(6):1045-57.

    4. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Ke Y, Chi L, Xu R, Luo C, Gozal D, Liu R Stem Cells. 2006 Apr; 24(4):1011-9.

    5. Bone marrow stromal cells for repair of the spinal cord: towards clinical application. Nandoe Tewarie RD, Hurtado A, Levi AD, Grotenhuis JA, Oudega M Cell Transplant. 2006; 15(7):563-77.

    6. Transplantation of adult rat spinal cord stem/progenitor cells for spinal cord injury. Parr AM, Kulbatski I, Tator CH J Neurotrauma. 2007 May; 24(5):835-45.

    7. Long-term results of spinal cord injury therapy using mesenchymal stem cells derived from bone marrow in humans. Park JH, Kim DY, Sung IY, Choi GH, Jeon MH, Kim KK, Jeon SR Neurosurgery. 2012 May; 70(5):1238-47; discussion 1247.

    8. Current Concept of Stem Cell Therapy for Spinal Cord Injury: A Review. Sun Kyu Oh, MD and Sang Ryong Jeon, MD, PhD. Korean J Neurotrauma. 2016 Oct; 12(2): 40–46.

  • Cerebral Palsy

    Cerebral palsy (CP) is a group of disorders of movement, muscle tone or posture due to damage occurred to the developing brain, usually before birth.  It causes impaired movement associated with abnormal reflexes, floppiness or rigidity of the limbs and trunk, abnormal posture, involuntary movements, unsteady walking, or some combination of these. Patients may develop problems in swallowing and usually have eye muscle imbalance due to which the eyes don't focus on the same object. They may also suffer reduced range of motion at various joints of their bodies due to muscular stiffness. The disorder’s effect on functional abilities varies broadly. Some patients can walk while others can't. Some show normal or near-normal intellectual capacity, but others may have intellectual problems. Epilepsy, blindness or deafness are sometimes present.

    Types of Cerebral Palsy

    Doctors classify CP according to the main type of movement disorder involved. Depending on which areas of the brain are affected, one or more of the following movement disorders can occur:

    • Stiff muscles (spasticity)

    • Uncontrollable movements (dyskinesia)

    • Poor balance and coordination (ataxia)

    There are four main types of CP:

    Spastic Cerebral Palsy

    The most common type of CP is spastic CP. Spastic CP affects about 80% of people with CP.

    People with spastic CP have increased muscle tone. This means their muscles are stiff and, as a result, their movements can be awkward. Spastic CP usually is described by what parts of the body are affected:

    Spastic diplegia/diparesis―In this type of CP, muscle stiffness is mainly in the legs, with the arms less affected or not affected at all. People with spastic diplegia might have difficulty walking because tight hip and leg muscles cause their legs to pull together, turn inward, and cross at the knees (also known as scissoring).

    Spastic hemiplegia/hemiparesis―This type of CP affects only one side of a person's body; usually the arm is more affected than the leg.

    Spastic quadriplegia/quadriparesis―Spastic quadriplegia is the most severe form of spastic CP and affects all four limbs, the trunk, and the face. People with spastic quadriparesis usually cannot walk and often have other developmental disabilities such as intellectual disability; seizures; or problems with vision, hearing, or speech.

    Dyskinetic Cerebral Palsy 

    People with dyskinetic CP have problems controlling the movement of their hands, arms, feet, and legs, making it difficult to sit and walk. The movements are uncontrollable and can be slow and writhing or rapid and jerky. Sometimes the face and tongue are affected and the person has a hard time sucking, swallowing, and talking. A person with dyskinetic CP has muscle tone that can change (varying from too tight to too loose) not only from day to day, but even during a single day.

    Ataxic Cerebral Palsy

    People with ataxic CP have problems with balance and coordination. They might be unsteady when they walk. They might have a hard time with quick movements or movements that need a lot of control, like writing. They might have a hard time controlling their hands or arms when they reach for something.

    Mixed Cerebral Palsy

    Some people have symptoms of more than one type of CP. The most common type of mixed CP is spastic-dyskinetic CP.

    Signs and Symptoms

    In a Baby Younger Than 6 Months of Age

    • His head lags when you pick him up while he’s lying on his back

    • He feels stiff

    • He feels floppy

    • When held cradled in your arms, he seems to overextend his back and neck, constantly acting as if he is pushing away from you

    • When you pick him up, his legs get stiff and they cross or scissor

    In a Baby Older Than 6 Months of Age

    • She doesn’t roll over in either direction

    • She cannot bring her hands together

    • She has difficulty bringing her hands to her mouth

    • She reaches out with only one hand while keeping the other fisted

    In a Baby Older Than 10 Months of Age

    • He crawls in a lopsided manner, pushing off with one hand and leg while dragging the opposite hand and leg

    • He scoots around on his buttocks or hops on his knees, but does not crawl on all fours

    Treatment 

    There is no cure for CP, but treatment can improve the lives of those who have the condition. It is important to begin a treatment program as early as possible.

    Role of Stem Cells in Cerebral Palsy

    Autologous bone marrow derived cells have been used to treat patients suffering from CP who reported significant improvement in the motor functions [1. 2]. In one report 85% improvement among cerebral palsy cases was observed, out of which 75% reported improvement in muscle tone and 50% in speech among other symptoms. No significant adverse events were noted. There was significant improvement of the quality of life as well [3]. There is scientific evidence that the growth factors similar to the ones released from the stem cells may help improve brain regeneration [4, 5].  There is the possibility that Transplanted bone marrow cells infiltrate the brain and may help regenerate new elements or combat the neurodegenerative process, fibrosis and oxidative insults. The result is potential repair of the damaged tissues [6].

    1. Therapeutic potential of autologous stem cell transplantation for cerebral palsy. Purandare C, Shitole DG, Belle V, Kedari A, Bora N, Joshi M Case Rep Transplant. 2012; 2012():825289.

    2. Safety and feasibility of autologous umbilical cord blood transfusion in 2 toddlers with cerebral palsy and the role of low dose granulocyte-colony stimulating factor injections. Papadopoulos KI, Low SS, Aw TC, Chantarojanasiri T Restor Neurol Neurosci. 2011; 29(1):17-22.

    3. Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Sharma A, Gokulchandran N, Chopra G, Kulkarni P, Lohia M, Badhe P, Jacob VC Cell Transplant. 2012; 21 Suppl 1():S79-90.

    4. Transplanted bone marrow generates new neurons in human brains. Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B Proc Natl Acad Sci U S A. 2003 Feb 4; 100(3):1364-9.

    5. The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia. Toth ZE, Leker RR, Shahar T, Pastorino S, Szalayova I, Asemenew B, Key S, Parmelee A, Mayer B, Nemeth K, Bratincsák A, Mezey E.Blood. 2008;111:5544–5552.

    6. The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J Immunology. 2009 Feb; 126(2):220-32.

  • Alzheimer's Disease (AD)

    Alzheimer’s Disease is the most common form of dementia and is characterized by the accumulation of amyloid plaques and neurofibrillary tangles accompanied by cognitive dysfunction. It is a progressive disease beginning with mild memory loss possibly leading to loss of the ability to carry on a conversation and respond to the environment. It Involves parts of the brain that control thought, memory, and language. It can seriously affect a person’s ability to carry out daily activities.

    Alzheimer’s disease is not a normal part of aging. Memory problems are typically one of the first warning signs of cognitive loss. In addition to memory problems, someone with Alzheimer’s disease may experience one or more of the following signs:

    • Gets lost.

    • Has trouble handling money and paying bills.

    • Repeats questions.

    • Takes longer to complete normal daily tasks.

    • Displays poor judgment.

    • Loses things or misplacing them in odd places.

    • Displays mood and personality changes.

    Treatment There is no known cure for Alzheimer’s disease although some medical management can improve the quality of life. Role of Stem Cells in Alzheimer’s disease Studies indicate that Mesenchymal Stem Cells alleviate Aβ deposition and memory deficits in AD model mice by modulating immune response [1]. The role of Intravenous Human Adipose-Derived Stem Cells in Alzheimer’s Disease has been shown in Mice. The report finds that hASCs prevent the onset and progression of the disease clearly provide an important preclinical platform for the development of prevention and therapy for AD patients [2]. Recently, mounting evidence has shown that successful treatment of AD can be achieved through the use of stem cells [3, 4]. Mesenchymal Stem Cells transplanted into the lateral ventricle migrated into the hippocampus, including the DG, and enhanced hippocampal neurogenesis [5]. Thus, the interaction between grafted MSCs and endogenous NSCs is crucial for attenuating the neuronal damage and loss observed in AD. In addition, MSCs might be able to protect AD brains from glutamate excitatory-induced apoptosis by secreting growth factors, activating the PI3K/Akt pathway, increasing anti-apoptotic factors and reducing caspase-3 activity [6].

    1. Lee JK, Jin HK, Endo S, Schuchman EH, Carter JE, et al. (2010) Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer’s disease mice by modulation of immune responses. Stem Cells 28: 329–343.

    2. Kim S, Chang K-A, Kim Ja, Park H-G, Ra JC, Kim H-S, et al. (2012) The Preventive and Therapeutic Effects of Intravenous Human Adipose-Derived Stem Cells in Alzheimer’s Disease Mice. PLoS ONE 7(9): e45757.

    3. Human umbilical cord blood-derived mesenchymal stem cells improve neuropathology and cognitive impairment in an Alzheimer's disease mouse model through modulation of neuroinflammation. Lee HJ, Lee JK, Lee H, Carter JE, Chang JW, Oh W, Yang YS, Suh JG , Lee BH, Jin HK, Bae JS Neurobiol Aging. 2012 Mar; 33(3):588-602.

    4. Progress in stem cell therapy for major human neurological disorders. Martínez-Morales PL, Revilla A, Ocaña I, González C, Sainz P, McGuire D, Liste I Stem Cell Rev. 2013 Oct; 9(5):685-99.

    5. Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior. Tfilin M, Sudai E, Merenlender A, Gispan I, Yadid G, Turgeman G Mol Psychiatry. 2010 Dec; 15(12):1164-75.

    6. Adipose-derived mesenchymal stem cells protect PC12 cells from glutamate excitotoxicity-induced apoptosis by upregulation of XIAP through PI3-K/Akt activation. Lu S, Lu C, Han Q, Li J, Du Z, Liao L, Zhao RC Toxicology. 2011 Jan 11; 279(1-3):189-95.

  • Parkinson's Disease (PD)

    Parkinson's disease is a progressive disorder of the nervous system that affects movement. It tends to develop gradually, sometimes starting with hardly noticeable tremor in just one hand. But while a tremor may be the most well-known sign of Parkinson's disease, the disorder also commonly causes stiffness or slowing of movement. Parkinson's disease symptoms worsen over time.

    Disease symptoms and signs may vary from person to person. Early signs may be mild and may go unnoticed. Symptoms often begin on one side of your body and usually remain worse on that side, even after symptoms begin to affect both sides.

    Parkinson's signs and symptoms may include:

    • Tremor
    • Slowed movement (bradykinesia)
    • Rigid muscles
    • Impaired posture and balance
    • Loss of automatic movements
    • Speech changes
    • Writing changes

    Treatment

    Parkinson's disease can't be cured, but certain medications can help control the symptoms. In some cases, surgery may be advised.

    Role of Stem Cells in Parkinson’s disease

    Numerous studies have shown that stem cells exert therapeutic effects in Parkinson’s Disease models [1-3]. Several stem cell sources for the treatment of PD have been studied in the past decades. These include adult bone marrow-derived mesenchymal stem cells (BM-MSC) and olfactory ensheathing cells (OEC) [4-5]. Studies have found that stem cells could be induced to generate dopaminergic neurons for an effective treatment of PD [6].

    1. Intrastriatal transplantation of mouse bone marrow-derived stem cells improves motor behavior in a mouse model of Parkinson's disease. Offen D, Barhum Y, Levy YS, Burshtein A, Panet H, Cherlow T, Melamed E J Neural Transm Suppl. 2007; (72):133-43.

    2. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease. Xiong N, Zhang Z, Huang J, Chen C, Zhang Z, Jia M, Xiong J, Liu X, Wang F, Cao X, Liang Z, Sun S, Lin Z, Wang T Gene Ther. 2011 Apr; 18(4):394-402.

    3. Neuroprotective effects of human umbilical cord mesenchymal stromal cells in an immunocompetent animal model of Parkinson's disease. Mathieu P, Roca V, Gamba C, Del Pozo A, Pitossi F J Neuroimmunol. 2012 May 15; 246(1-2):43-50.

    4. Transplantation of neuronal-primed human bone marrow mesenchymal stem cells in hemiparkinsonian rodents. Khoo ML, Tao H, Meedeniya AC, Mackay-Sim A, Ma DD PLoS One. 2011; 6(5):e19025.

    5. Enhanced survival and function of neural stem cells-derived dopaminergic neurons under influence of olfactory ensheathing cells in parkinsonian rats. Shukla S, Chaturvedi RK, Seth K, Roy NS, Agrawal AK J Neurochem. 2009 Apr; 109(2):436-51.

    6. Kitada M, Dezawa M. Parkinson's disease and mesenchymal stem cells: potential for cell-based therapy. Parkinson's disease. 2012;2012

  • Amyotrophic lateral sclerosis

    ALS is a progressive nervous system (neurological) disease that destroys nerve cells and causes disability. It usually begins with muscle twitching and weakness in a limb or slurred speech. It affects control of the muscles needed to move, speak, eat and breathe.

    Some symptoms of ALS include:

    · Difficulty in walking or doing normal daily activities

    · Tripping and falling

    · Weakness in legs, feet or ankles

    · Hand weakness or clumsiness

    · Slurred speech or trouble swallowing

    · Muscle cramps and twitching in arms, shoulders and tongue

    · Difficulty holding head up or keeping good posture

    In later stages, complications like problems in breathing, speaking and eating may happen. Sometimes dementia is also experienced.

    Treatment

    Treatments can't reverse the damage of caused by amyotrophic lateral sclerosis, but they can slow the progression of symptoms and prevent complications.

    Role of Stem Cells in ALS

    Preclinical in vitro and in vivo studies have provided tremendous insight into the role of stem cells in ALS [1, 2]. Retro-orbital delivery of stem cells improved neuromuscular transmission [3], and intravenous stem cells administration delayed disease progression by 15%, induced anti-inflammatory effects, reduced microglial activation, and increased survival up to 20-25% in G93A-SOD1 mice model. [4, 5]. Although the age of stem cell-based therapeutics is just beginning, a handful of cellular therapy trials for ALS have been completed in different countries around the world. These recent trials include vast differences in the number of patients, cell type, delivery method, and outcome measurement strategies; however, each study has the potential to contribute to our current understanding of the safety and feasibility of stem cell therapies for ALS, as these variables provide important considerations for future trial design and clinical application.

    1. Translational stem cell therapy for amyotrophic lateral sclerosis. Boulis NM, Federici T, Glass JD, Lunn JS, Sakowski SA, Feldman EL Nat Rev Neurol. 2011 Dec 13; 8(3):172-6.

    2. Stem cell technology for the study and treatment of motor neuron diseases. Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL Regen Med. 2011 Mar; 6(2):201-13.

    3. Defective neuromuscular transmission in the SOD1 G93A transgenic mouse improves after administration of human umbilical cord blood cells. Souayah N, Coakley KM, Chen R, Ende N, McArdle JJ Stem Cell Rev. 2012 Mar; 8(1):224-8.

    4. Human umbilical cord blood treatment in a mouse model of ALS: optimization of cell dose. Garbuzova-Davis S, Sanberg CD, Kuzmin-Nichols N, Willing AE, Gemma C, Bickford PC, Miller C, Rossi R, Sanberg PR PLoS One. 2008 Jun 25; 3(6):e2494.

    5. Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: distribution, migration, and differentiation. Garbuzova-Davis S, Willing AE, Zigova T, Saporta S, Justen EB, Lane JC, Hudson JE, Chen N, Davis CD, Sanberg PR J Hematother Stem Cell Res. 2003 Jun; 12(3):255-70.

  • Arthritis

    Arthritis means inflammation of a joint or joints. Inflamed joints are often red, hot, swollen, and tender. It describes more than 100 conditions that affect the joints or tissues around the joint. Specific symptoms vary depending on the type of arthritis.

    Rheumatoid arthritis or RA mainly attacks the joints, usually many joints at once. In a joint with RA, the lining of the joint becomes inflamed, causing damage to joint tissue that can result in long-lasting or chronic pain, instability, and deformity.

    RA can also have systemic effects, meaning that, in addition to joints, it can affect other tissues throughout the body and cause problems in organs such as the lungs, heart, and eyes.

    With RA, there are times when symptoms get worse, known as flares, and times when symptoms get better, known as remissions. The severity of RA varies.

    Symptoms may include:

    • Pain or aching in more than one joint

    • Stiffness in more than one joint.

    • Tender, swollen joints.

    • Weight loss.

    • Fatigue, or tiredness.

    • Fever.

    Osteoarthritis (OA) is the most common form of arthritis. The cartilage and bones within a joint begin to break down in people with OA. These changes cause pain, stiffness, and even disability. OA usually develops slowly and gets worse over time.

    Symptoms may include:

    • Pain or aching

    • Stiffness.

    • Decreased range of motion.

    • Swelling

    Treatment

    The treatment for arthritis is to control pain, minimize joint damage, and improve or maintain function and quality of life.

    Role of Stem Cells in Arthritis

    The potential application of stem cells transplantation in the treatment of Rheumatoid Arthritis was first suggested by preclinical observations on inducible (acute arthritis) animal models of autoimmune disease [1]. Because of their regenerative and immuno-modulatory properties, MSC therapy has been the focus of several investigations as potential therapeutic tools to correct the aberrant immune tolerance both in animal models of inflammatory arthritis and in RA patients. A total of 136 RA patients in two trials with active disease were enrolled in a single-center phase I/II study and treated with intravenous injection of UC-MSCs and DMARDs. The procedure was shown to be safe, as no serious adverse effects were observed, and significant remission was achieved in comparison to the non-randomized control group of 36 patients receiving only DMARDs and cell medium. The clinical improvement correlated with decreased expression of inflammatory cytokines and increased presence of regulatory T cells in peripheral blood, and was maintained up to 3–6 months without continuous administration [2].

    Several studies have focused on cell-based therapy for joint surface defects and Osteoarthritis (OA) using mature cells (chondrocytes) and stem cells, because it could offer a long-term solution to repair and regenerate cartilage, improve symptoms and delay disease progression [3]. There has been an increasing trend to localized stem cell delivery via minimally invasive intra-articular injections. Several case reports have described the outcomes of direct intra-articular injection of MSCs into the knee of OA patients unresponsive to conventional treatment [4, 5].

    1. Regression of adjuvant-induced arthritis in rats following bone marrow transplantation.van Bekkum DW, Bohre EP, Houben PF, Knaan-Shanzer S Proc Natl Acad Sci U S A. 1989 Dec; 86(24):10090-4.

    2. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Wang L, Wang L, Cong X, Liu G, Zhou J, Bai B, Li Y, Bai W, Li M, Ji H, Zhu D, Wu M, Liu Y Stem Cells Dev. 2013 Dec 15; 22(24):3192-202.

    3. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Wakitani S, Imoto K, Yamamoto T, Saito M, Murata N, Yoneda M Osteoarthritis Cartilage. 2002 Mar; 10(3):199-206.

    4. Orozco L, Munar A, Soler R, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells. Transplant J 2013; 95: 1535–1541.

    5. Rich SR, Romagosa SF, Sancho GJ, et al. Stem cell treatment of knee osteoarthritis with autologous expanded bone marrow mesenchymal stem cells: 50 cases clinical and MRI results at one year follow-up. J Stem Cell Res Ther.

  • Systemic lupus erythematosus (SLE)

    Systemic lupus erythematosus also known as SLE, is an autoimmune inflammatory disease, which means that the immune system attacks healthy cells in the body by mistake, causing inflammation in the affected parts of the body.

    SLE is systemic, meaning that it affects multiple systems in the body. The disease is usually long-term or chronic, with times when symptoms get worse, known as flares, and times when symptoms get better, known as remissions.

    Symptoms may include:

    · Joint pain.

    · Skin rashes.

    · Nervous system problems like seizures.

    · Oral ulcers.

    · Photosensitivity (sensitivity to light).

    Role of Stem Cells in Arthritis

    BM-MSCs and UC-MSCs have been transplanted in patients with severe SLE, who were not responsive to conventional therapies. The 4-year follow-up demonstrated that about 50 % of the patients entered clinical remission after transplantation, although 23 % of the patients relapsed [1]. MSC infusion induced disease remission for lupus nephritis [2], diffuse alveolar hemorrhage [3], and refractory cytopenia [4]. The multi-center clinical study showed that 32.5 % of patients achieved major clinical response (13 out of 40) and 27.5 % of patients achieved partial clinical response (11 out of 40) during a 12-month follow-up, respectively. However, 7 (17.5 %) out of 40 patients experienced a disease relapse after 6 months of follow-up, after a prior clinical response, which indicated that another MSC infusion would be necessary after 6 months [5].

    1. Allogeneic mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus: 4 years of experience. Wang D, Zhang H, Liang J, Li X, Feng X, Wang H, Hua B, Liu B, Lu L, Gilkeson GS, Silver RM, Chen W, Shi S, Sun L Cell Transplant. 2013; 22(12):2267-77.

    2. Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X, Xu W, Zeng X, Hou Y, Gilkeson GS, Silver RM, Lu L, Shi S Arthritis Rheum. 2010 Aug; 62(8):2467-75.

    3. Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Shi D, Wang D, Li X, Zhang H, Che N, Lu Z, Sun L Clin Rheumatol. 2012 May; 31(5):841-6.

    4. Mesenchymal SCT ameliorates refractory cytopenia in patients with systemic lupus erythematosus. Li X, Wang D, Liang J, Zhang H, Sun L Bone Marrow Transplant. 2013 Apr; 48(4):544-50.

    5. Umbilical cord mesenchymal stem cell transplantation in active and refractory systemic lupus erythematosus: a multicenter clinical study. Wang D, Li J, Zhang Y, Zhang M, Chen J, Li X, Hu X, Jiang S, Shi S, Sun L Arthritis Res Ther. 2014 Mar 25; 16(2):R79.

  • Stroke

    A stroke, sometimes called a brain attack, occurs when something blocks blood supply to part of the brain or when a blood vessel in the brain bursts. In either case, parts of the brain become damaged or die. A stroke can cause lasting brain damage, long-term disability, or even death.

    There are two types of stroke:

    · An ischemic stroke occurs when blood clots or other particles block the blood vessels to the brain. Fatty deposits called plaque can also cause blockages by building up in the blood vessels.

    · A hemorrhagic stroke occurs when a blood vessel bursts in the brain. Blood builds up and damages surrounding brain tissue.

    Both types of stroke damage brain cells. Symptoms of that damage start to show in the parts of the body controlled by those brain cells.

    Symptoms of Stroke

    · Sudden numbness or weakness in the face, arm, or leg, especially on one side of the body

    · Sudden confusion, trouble speaking, or difficulty understanding speech

    · Sudden trouble seeing in one or both eyes

    · Sudden trouble walking, dizziness, loss of balance, or lack of coordination

    · Sudden severe headache with no known cause

    Role of Stem Cells in Stroke

    MSCs may be a good choice for stroke therapy because they secrete a variety of bioactive substances, including trophic factors and extracellular vesicles (EVs, 0.1–1 μm sized circular membrane fragments shed from the cell surface), into the injured brain, which may be associated with enhanced neurogenesis, angiogenesis, and synaptogenesis [1-4]. Several clinical trials of stem cell therapy were conducted in patients with stroke. Most clinical trials used adult stem cells, such as MSCs [5,6] and bone marrow mononuclear cells [7,8].

    1. Li WY, Choi YJ, Lee PH, Huh K, Kang YM, Kim HS, et al. Mesenchymal stem cells for ischemic stroke: changes in effects after ex vivo culturing. Cell Transplant. 2008;17:1045–1059.

    2. Liu Z, Li Y, Zhang RL, Cui Y, Chopp M. Bone marrow stromal cells promote skilled motor recovery and enhance contralesional axonal connections after ischemic stroke in adult mice. Stroke. 2011;42:740–744.

    3. Song M, Mohamad O, Gu X, Wei L, Yu SP. Restoration of intracortical and thalamocortical circuits after transplantation of bone marrow mesenchymal stem cells into the ischemic brain of mice. Cell Transplant. 2013;22:2001–2015.

    4. Chen X, Li Y, Wang L, Katakowski M, Zhang L, Chen J, et al. Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology. 2002;22:275–279.

    5. Autologous mesenchymal stem cell transplantation in stroke patients. Bang OY, Lee JS, Lee PH, Lee G Ann Neurol. 2005 Jun; 57(6):874-82.

    6. Hess DC, Auchus AP, Uchino K, Sila C, Clark WM, Chiu D, et al. Final results of the B01-02 phase 2 trial testing the safety and efficacy of MultiStem® in treatment of ischemic stroke. International Stroke Conference; LA. 2016.

    7. Autologous bone marrow stem cell neurotransplantation in stroke patients. An open study. Suárez-Monteagudo C, Hernández-Ramírez P, Alvarez-González L, García-Maeso I, de la Cuétara-Bernal K, Castillo-Díaz L, Bringas-Vega ML, Martínez-Aching G, Morales-Chacón LM, Báez-Martín MM, Sánchez-Catasús C, Carballo-Barreda M, Rodríguez-Rojas R, Gómez-Fernández L, Alberti-Amador E, Macías-Abraham C, Balea ED, Rosales LC, Del Valle Pérez L, Ferrer BB, González RM, Bergado JA Restor Neurol Neurosci. 2009; 27(3):151-61.

    8. Intravenous autologous bone marrow mononuclear stem cell therapy for ischemic stroke: a multicentric, randomized trial. Prasad K, Sharma A, Garg A, Mohanty S, Bhatnagar S, Johri S, Singh KK, Nair V, Sarkar RS, Gorthi SP, Hassan KM, Prabhakar S, Marwaha N, Khandelwal N, Misra UK, Kalita J, Nityanand S, InveST Study Group. Stroke. 2014 Dec; 45(12):3618-24.

  • Diabetes

    Diabetes is a chronic (long-lasting) disease that affects how body turns food into energy. Most of the food we eat is broken down into sugar (also called glucose) and released into our bloodstream. Our pancreas makes a hormone called insulin, which acts like a key to allow the blood sugar into our body’s cells for use as energy.

    If we have diabetes, our body either doesn’t make enough insulin or can’t use the insulin it makes as well as it should. When there isn’t enough insulin or cells stop responding to insulin, too much blood sugar stays in our bloodstream, which over time can cause serious health problems, such as heart disease, vision loss, and kidney disease.

    There are three main types of diabetes: type 1, type 2, and gestational diabetes (diabetes while pregnant).

    Type 1 diabetes is caused by an autoimmune reaction (the body attacks itself by mistake) that stops our body from making insulin. About 5% of the people who have diabetes have type 1. Symptoms of type 1 diabetes often develop quickly. It’s usually diagnosed in children, teens, and young adults. If we have type 1 diabetes, we’ll need to take insulin every day to survive. Currently, no one knows how to prevent type 1 diabetes.

    With Type 2 diabetes, our body doesn’t use insulin well and is unable to keep blood sugar at normal levels. Most people with diabetes—9 in 10—have type 2 diabetes. It develops over many years and is usually diagnosed in adults (though increasingly in children, teens, and young adults). We may not notice any symptoms, so it’s important to get our blood sugar tested if we’re at risk. Type 2 diabetes can be prevented or delayed with healthy lifestyle changes, such as losing weight if you’re overweight, healthy eating, and getting regular physical activity.

    Gestational diabetes develops in pregnant women who have never had diabetes. If you have gestational diabetes, your baby could be at higher risk for health complications. Gestational diabetes usually goes away after your baby is born but increases your risk for type 2 diabetes later in life. Your baby is more likely to become obese as a child or teen, and more likely to develop type 2 diabetes later in life too.

    Symptoms of Diabetes

    • Urinate (pee) a lot, often at night
    • Are very thirsty
    • Lose weight without trying
    • Are very hungry
    • Have blurry vision
    • Have numb or tingling hands or feet
    • Feel very tired
    • Have very dry skin
    • Have sores that heal slowly
    • Have more infections than usual

    Treatment

    Diabetes cannot be cured but managed with medications, lifestyle changes, food habits, exercises and in extreme cases by taking insulin.

     

    Role of Stem Cells in Diabetes

    Clinical trial was carried out in patients with new onset Type 1 DM suggested that MSC therapy can provide sustained, long term functional improvement [1]. In another 6 studies involving 146 patients undergoing stem cells therapy 58.9% became insulin-free for a mean period of 16 months and in 7.53% the insulin requirement was reduced by more than 50% [2-5]. In Type 2 DM the clinical data suggested that UC-MSC treatment provided a long lasting therapeutic effect [6].

    1. Long term effects of the implantation of Wharton's jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Hu J, Yu X, Wang Z, Wang F, Wang L, Gao H, Chen Y, Zhao W, Jia Z, Yan S, Wang Y Endocr J. 2013; 60(3):347-57.

    2. C-peptide levels and insulin independence following autologous nonmyeloablative hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus. Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F, Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simões BP, Martinez EZ, Foss MC, Burt RK, Voltarelli JC JAMA. 2009 Apr 15; 301(15):1573-9.

    3. Autologous nonmyeloablative hematopoietic stem cell transplantation in new-onset type 1 diabetes: a multicenter analysis. D'Addio F, Valderrama Vasquez A, Ben Nasr M, Franek E, Zhu D, Li L, Ning G, Snarski E, Fiorina P Diabetes. 2014 Sep; 63(9):3041-6.

    4. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes. Li L, Shen S, Ouyang J, Hu Y, Hu L, Cui W, Zhang N, Zhuge YZ, Chen B, Xu J, Zhu D J Clin Endocrinol Metab. 2012 May; 97(5):1729-36.

    5. Acute response of peripheral blood cell to autologous hematopoietic stem cell transplantation in type 1 diabetic patient. Zhang X, Ye L, Hu J, Tang W, Liu R, Yang M, Hong J, Wang W, Ning G, Gu W PLoS One. 2012; 7(2):e31887.

    6. A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Liu X, Zheng P, Wang X, Dai G, Cheng H, Zhang Z, Hua R, Niu X, Shi J, An Y Stem Cell Res Ther. 2014 Apr 23; 5(2):57.

  • Autism

    Role of Stem Cells in Autism

    ASD patients show an imbalance in CD3+, CD4+, and CD8+ T cells, as well as in NK cells. In addition, peripheral blood mononuclear cells (PBMCs) extracted from ASD patients are able to overproduce IL-1β resulting in long-term immune alterations [1]. MSC-mediated immune suppressive activity could restore this immune imbalance and infact MSC immunoregulatory effects strongly inhibit T-cell recognition and expansion by inhibiting TNF-α and INF-γproduction and increasing IL-10 levels [2]. In ASD therapy, MSC-mediated immune system modulating activity could be a key mechanism.

     

    1. Differential monocyte responses to TLR ligands in children with autism spectrum disorders. Enstrom AM, Onore CE, Van de Water JA, Ashwood P Brain Behav Immun. 2010 Jan; 24(1):64-71.

    2.Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Meirelles Lda S, Fontes AM, Covas DT, Caplan AI Cytokine Growth Factor Rev. 2009 Oct-Dec; 20(5-6):419-27.