Stem Cell Research Articles


Stem cell therapy is a fascinating field of medicine with enormous amounts of research devoted to its advancement. We have pulled together a group of relevant scientific publications for those who are interested in a deeper review. Below is a list stem cell research articles to help you gain additional insight into the ongoing studies. Research conclusions bring clarity into persisting stem cell myths.

Adipose-Derived Adult Stem Cells and New Technique for Intracavernosal Injection for Erectile Dysfunction: Novel Approach to Treat Diabetes Mellitus. Erectus Shot Technique

PUBLISHED in Integrative Molecular Medicine Medicine, 2016, Vol 3(2)   AUTHOR Carlos Mercado, MD

Erectile Dysfunction (ED) affects 10 percent of the population worldwide. In 1995 it was estimated that 152 million men were affected by ED. It is estimated that by 2025 352 million of population worldwide will be affected. Currently there is not available treatment that can restore or regenerate the tissues in the corpus cavernosum or arterial system tthat will cure ED a 20 percent failure rate with present therapies and high rate of drop out in patients with ED due to radical prostatectomy and post radiation. Testosterone eplacement is the only independent risk factor that might help endothelial dysfunction and consequently ED. Adipose tissue is abundant and easy to collect from a miniliposuction. The procedure consists in collecting a lipoaspirate of 60 ml. No general Anesthesia is required. It is an outpatient procedure. Adipose tissue is processed using a non animal collagenase enzyme. Stromal vascular fraction (SVF) is isolated. Blood is obtained through a venipuncture. Platelet rich-plasma (PRP) is obtained. The SVF is suspended in PRP. The mixture is injected into the corpus cavernosum using our designed protocol for injection.

Four types of patients: DM, ED due to prostatectomy and radiation, Peyronie’s disease, and ED organic cause/aging/vascular. Patients filled out the intensity score questionnaire before and after procedure. Both reported better erections in the morning, firmer, and better response to PDI5 inhibitors for which they were not responders prior to the treatment. This might be due to stem cells induced regeneration of the cavernous nerve and endothelial cells enhancing the nitric oxide production hence improved response to PDI-5 inhibitors.

Abandoning Microfracture of the Knee: Has the Time Come?

PUBLISHED on The Journal of Arthroscopic and Related Surgery, 2015   AUTHORS Jack M. Bert, M.D.

Marrow stimulation has been performed for more than 45 years beginning with the simple drilling of bony surfaces, burring or “abrading” the sclerotic lesion, and more recently using awls to penetrate eburnated bone to promote blood flow to the bony surface. Multiple authors have promoted these procedures as “helpful,” but others have confirmed only short-term relief with destruction of the subchondral surface. Unfortunately, proponents do not compare their marrow stimulation results to a control group that had debridement alone. A recent study confirmed that microfracture (MF) is equivalent to debridement and does not affect the subchondral bone, which therefore does not reduce the success rates of future surgery subsequent to MF. This brief review summarizes some of the factual data showing that marrow stimulation may not offer any improvement over debridement alone and that, in fact, MF results in significant destruction to the subchondral bone.

Regenerative Repair of Damaged Meniscus with Autologous Adipose Tissue-Derived Stem Cells

PUBLISHED on BioMed Research International by Jaewoo Pak et al., 2014.   AUTHORS Jaewoo Pak, Jung Hun Lee and Sang Hee Lee.

Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

Intra-Articular Injection of Mesenchymal Stem Cells for the Treatment of Osteoarthritis of the Knee: a Proof-of-Concept Clinical Trial

PUBLISHED on Wiley Online Library by AlphaMed Press, 2014.   AUTHORS Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS.

 KEYWORDS Adipose-tissue derived mesenchymal stem cells; Cartilage regeneration; Intra-articular injection; Osteoarthritis.

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 × 10(7) cells), mid-dose (5.0 × 10(7)), and high-dose (1.0 × 10(8)) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 × 10(8) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.

Stem Cell Therapy Following Meniscus Knee Surgery May Reduce Pain, Restore Meniscus

PUBLISHED on Digital Journal by The American Academy of Orthopaedic Surgeons (AAOS), 2014.

Key Study Findings

  • There was no abnormal (ectopic) tissue formation or “clinically important” safety issues identified.
  • There was “significantly increased meniscal volume,” determined by an MRI in 24 percent of the patients in the low-dose injection group (A) and six percent of the high-dose injection group (B) at one year. There was no statistical increase in meniscal volume at two years.
  • No patients in the control group (non-MSC group) met the 15 percent threshold for increased meniscal volume.
  • Patients with osteoarthritis experienced a reduction in pain in the stem cell treatment groups; there was no reduction in pain in the control (non-MSC group).

Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy

PUBLISHED in The Journal of Bone & Joint Surgery Inc., 2014.   AUTHORS ; ; ; ; ; .

Background: There are limited treatment options for tissue restoration and the prevention of degenerative changes in the knee. Stem cells have been a focus of intense preclinical research into tissue regeneration but limited clinical investigation. In a randomized, double-blind, controlled study, the safety of the intra-articular injection of human mesenchymal stem cells into the knee, the ability of mesenchymal stem cells to promote meniscus regeneration following partial meniscectomy, and the effects of mesenchymal stem cells on osteoarthritic changes in the knee were investigated.

Methods: A total of fifty-five patients at seven institutions underwent a partial medial meniscectomy. A single superolateral knee injection was given within seven to ten days after the meniscectomy. Patients were randomized to one of three treatment groups: Group A, in which patients received an injection of 50 × 106 allogeneic mesenchymal stem cells; Group B, 150 × 106 allogeneic mesenchymal stem cells; and the control group, a sodium hyaluronate (hyaluronic acid/hyaluronan) vehicle control. Patients were followed to evaluate safety, meniscus regeneration, the overall condition of the knee joint, and clinical outcomes at intervals through two years. Evaluations included sequential magnetic resonance imaging (MRI).

Results: No ectopic tissue formation or clinically important safety issues were identified. There was significantly increased meniscal volume (defined a priori as a 15% threshold) determined by quantitative MRI in 24% of patients in Group A and 6% in Group B at twelve months post meniscectomy (p = 0.022). No patients in the control group met the 15% threshold for increased meniscal volume. Patients with osteoarthritic changes who received mesenchymal stem cells experienced a significant reduction in pain compared with those who received the control, on the basis of visual analog scale assessments.

Conclusions: There was evidence of meniscus regeneration and improvement in knee pain following treatment with allogeneic human mesenchymal stem cells. These results support the study of human mesenchymal stem cells for the apparent knee-tissue regeneration and protective effects.

You May Not Be Better Off After Knee Surgery

PUBLISHED on CNN.com, 2013.   AUTHORS 

Patients who underwent simulated knee surgery fared just as well as those who got the real deal, according to a new study that’s raising eyebrows about the most common orthopedic procedure performed in the United States.

Arthroscopic Partial Meniscectomy versus Sham Surgery for a Degenerative Meniscal Tear

PUBLISHED in The New England Journal of Medicine by the Finnish Degenerative Meniscal Lesion Study (FIDELITY) Group, 2013.   AUTHORS Raine Sihvonen, M.D., Mika Paavola, M.D., Ph.D., Antti Malmivaara, M.D., Ph.D., Ari Itälä, M.D., Ph.D., Antti Joukainen, M.D., Ph.D., Heikki Nurmi, M.D., Juha Kalske, M.D., and Teppo L.N. Järvinen, M.D., Ph.D.

 BACKGROUND: Arthroscopic partial meniscectomy is one of the most common orthopedic procedures, yet rigorous evidence of its efficacy is lacking.

METHODS: We conducted a multicenter, randomized, double-blind, sham-controlled trial in 146 patients 35 to 65 years of age who had knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis. Patients were randomly assigned to arthroscopic partial meniscectomy or sham surgery. The primary outcomes were changes in the Lysholm and Western Ontario Meniscal Evaluation Tool (WOMET) scores (each ranging from 0 to 100, with lower scores indicating more severe symptoms) and in knee pain after exercise (rated on a scale from 0 to 10, with 0 denoting no pain) at 12 months after the procedure.

RESULTS: In the intention-to-treat analysis, there were no significant between-group differences in the change from baseline to 12 months in any primary outcome. The mean changes (improvements) in the primary outcome measures were as follows: Lysholm score, 21.7 points in the partial-meniscectomy group as compared with 23.3 points in the sham-surgery group (between-group difference, −1.6 points; 95% confidence interval [CI], −7.2 to 4.0); WOMET score, 24.6 and 27.1 points, respectively (between-group difference, −2.5 points; 95% CI, −9.2 to 4.1); and score for knee pain after exercise, 3.1 and 3.3 points, respectively (between-group difference, −0.1; 95% CI, −0.9 to 0.7). There were no significant differences between groups in the number of patients who required subsequent knee surgery (two in the partial-meniscectomy group and five in the sham-surgery group) or serious adverse events (one and zero, respectively).

CONCLUSIONS: In this trial involving patients without knee osteoarthritis but with symptoms of a degenerative medial meniscus tear, the outcomes after arthroscopic partial meniscectomy were no better than those after a sham surgical procedure. (Funded by the Sigrid Juselius Foundation and others; ClinicalTrials.gov number, NCT00549172.)

Treatment of Knee Osteoarthritis with Autologous Mesenchymal Stem Cells: a Pilot Study

PUBLISHED in The Transplantation Journal, 2013.   AUTHORS Orozco, Lluis; Munar, Anna; Soler, Robert; Alberca, Mercedes; Soler, Francesc; Huguet, Marina; Sentís, Joan; Sánchez, Ana; García-Sancho, Javier

 BACKGROUND: Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain, functional loss, and disability. Osteoarthritis often becomes chronic, and conventional treatments have demonstrated only modest clinical benefits without lesion reversal. Cell-based therapies have shown encouraging results in both animal studies and a few human case reports. We designed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells (MSCs) in humans and to obtain early efficacy information for this treatment.

METHODS: Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous expanded bone marrow MSCs by intra-articular injection (40×10 cells). Clinical outcomes were followed for 1 year and included evaluations of pain, disability, and quality of life. Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping.

RESULTS: Feasibility and safety were confirmed, and strong indications of clinical efficacy were identified. Patients exhibited rapid and progressive improvement of functional indices that approached 65% to 78% by 1 year. This outcome compares favorably with the results of conventional treatments. Additionally, quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas (on average, 27%), with improvement of cartilage quality in 11 of the 12 patients.

CONCLUSIONS: MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis. The intervention is simple, does not require hospitalization or surgery, provides pain relief, and significantly improves cartilage quality.

Millennium Medical Technologies – Statement of Position towards FDA’s Stance on Stem Cell Therapy

 PUBLISHED on millenniummedicaltechnologies.com, 2013.   AUTHORS David Angeloni

Millennium Medical Technologies is committed to further advance our core values related to the use of Adipose Derived Cells and Platelet Rich Plasma around our evidence based processes. We feel these procedures are paramount in contributing to better outcomes. It is our opinion that our component based system of FDA registered or compliant products allow a physician to practice medicine, within their own scope of expertise, using ADC’s and PRP without “minimal manipulation” and “homologous use” concerns as you are complying with cGTP. Certainly the physician shouldn’t advertise “treatment claims” with any autologous stem cells harvested/isolated in such a manner but we support and believe a physician may legally use them as a tool in their practice.

No Such Thing as Stem Cells in a Bottle

PUBLISHED in Philippine Daily Inquirer, 2013.   AUTHORS Cheche V. Moral

Philippines – The Department of Health and some medical organizations are calling for a clampdown on hospitals, clinics and centers offering stem cell treatments. But instead of being discouraged, one of stem cell therapy’s vocal advocates and practitioners in the country said she welcomes the move.

FDA Regulations of Stem Cell Therapy

PUBLISHED on fda.gov, 2014.

TITLE 21–FOOD AND DRUGS

CHAPTER I–FOOD AND DRUG ADMINISTRATION

DEPARTMENT OF HEALTH AND HUMAN SERVICES

SUBCHAPTER L–REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION

PART 1271–HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS

Adipose-Derived Stem Cells for Regenerative Medicine

PUBLISHED in Circulation Research by American Heart Association, 2007.   AUTHORS Jeffrey M. GimbleAdam J. Katz, Bruce A. Bunnell

KEYWORDS adipose tissue, adult stem cells, bone marrow stromal cell, differentiation, tissue engineering

The emerging field of regenerative medicine will require a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate along multiple lineage pathways. The isolation, characterization, and preclinical and clinical application of adipose-derived stem cells (ASCs) are reviewed in this article.

Adipose-Derived Stem Cells: Characterization and Current Application in Orthopaedic Tissue Repair

PUBLISHED in Experimental Biology and Medicine, 2008.   AUTHORS Hazel Tapp, Edward N. Hanley Jr., Joshua C. Patt, Helen E. Gruber

KEYWORDS adipose-derived stem cells, orthopaedic tissue regeneration, cell-surface markers, differentiation

Orthopaedic tissues, such as bone, cartilage, intervertebral disc and tendon, contain cells that are difficult to culture and stimulate in vitro for repair of damaged tissue. Stem cells have the ability to self-renew and differentiate into many tissue types. Recent progress in stem cell research has led to an enthusiastic effort to utilize stem cells for orthopaedic tissue regeneration. Due to ease of harvest and abundance, adipose-derived mesenchymal cells (ASC) are an attractive, readily available adult stem cell that has become increasingly popular for use in many stem cell applications. Recent progress has been made in characterizing ASC and looking mechanistically at gene expression and cellular pathways involved in differentiation. This review focuses on (i) the characterization of ASC through expression of appropriate surface markers; (ii) modulation of in vitro differentiation of ASC through different scaffolds, growth factors, and media; and (iii) the use of ASC in orthopaedic tissue repair. Strategies for repair involve the use of differentiated or undifferentiated, fresh or passaged ASC, in conjunction with appropriate choice of media, growth factors and scaffolds. Recent in vivo studies utilizing ASC are discussed giving results on defect repair and potential for clinical orthopaedic tissue regeneration.

Human Adipose Stem Cells: Current Clinical Applications

PUBLISHED in Journal of American Society of Plastic Surgeons, 2012.   AUTHORS Gir, Phanette M.D.; Oni, Georgette M.D.; Brown, Spencer A. Ph.D.; Mojallal, Ali M.D., Ph.D.; Rohrich, Rod J. M.D.

Adipose-derived stem cells are multipotent cells that can easily be extracted from adipose tissue, are capable of expansion in vitro, and have the capacity to differentiate into multiple cell lineages, which have the potential for use in regenerative medicine. However, several issues need to be studied to determine safe human use. For example, there are questions related to isolation and purification of adipose-derived stem cells, their effect on tumor growth, and the enforcement of U.S. Food and Drug Administration regulations. Numerous studies have been published, with the interest in the potential for regenerative medicine continually growing. Several clinical trials using human adipose stem cell therapy are currently being performed around the world, and there has been a rapid evolution and expansion of their number. The purpose of this article was to review the current published basic science evidence and ongoing clinical trials involving the use of adipose-derived stem cells in plastic surgery and in regenerative medicine in general. The results of the studies and clinical trials using adipose-derived stem cells reported in this review seem to be promising not only in plastic surgery but also in a wide variety of other specialties. Nevertheless, those reported showed disparity in the way adipose-derived stem cells were used. Further basic science experimental studies with standardized protocols and larger randomized trials need to be performed to ensure safety and efficacy of adipose-derived stem cells use in accordance with U.S. Food and Drug Administration guidelines.

Human Adipose Tissue Is a Source of Multipotent Stem Cells

PUBLISHED in Molecular Biology of the Cell, 2002.   AUTHORS Patricia A. ZukMin ZhuPeter AshjianDaniel A. De UgarteJerry I. HuangHiroshi MizunoZeni C. AlfonsoJohn K. FraserProsper Benhaim and Marc H. Hedrick

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

President Obama and the Embryonic Backfire

PUBLISHED on Huffington Post, 2013.   AUTHORS Robin L. Smith

It is exceptionally hard to cut through embryonic misperceptions that exist in the financial marketplace. And when you consider that biomedical and health R&D spending in the United States fell by more than $4 billion in fiscal 2011, we face an uphill battle in the years ahead in our quest to turn cells into conduits of hope and healing.

Adult Mesenchymal Stem Cells: an Innovative Therapeutic for Lung Diseases

PUBLISHED in Discovery Medicine, 2010.   AUTHORS Tracey L. Bonfield, Arnold I. Caplan

Adult human mesenchymal stem cells (hMSCs) are the focus of a number of clinical applications. The advantage of hMSCs is that they are immuno-modulatory and versatile due to their secreted bioactive molecules that are anti-inflammatory and regenerative. These cells have the potential to orchestrate reparative processes in diseased or injured tissues. Much of the diversity and uniqueness of hMSCs is defined by their response to the milieu of injured tissue. hMSCs are sensitive to their site-specific microenvironment, and it is anticipated that they will deliver the bioactive agents in a site-specific manner quite different from the way pharmaceutical drugs work. This review highlights current concepts of such functions with a focus on the clinical utility of hMSCs in the treatment of lung diseases.

Potential Role of Stem Cells in Management of COPD

PUBLISHED in International Journal of COPD, 2010.   AUTHORS Tillie L Hackett, Darryl A Knight, and Don D Sin

 COPD, stem cell therapy, epithelial repair, regenerative medicine

Chronic obstructive pulmonary disease (COPD) is a worldwide epidemic affecting over 200 million people and accounting for more than three million deaths annually. The disease is characterized by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Unfortunately, there are no interventions that have been unequivocally shown to prolong survival in patients with COPD. Regeneration of lung tissue by stem cells from endogenous and exogenous sources is a promising therapeutic strategy. Herein we review the current literature on the characterization of resident stem and progenitor cell niches within the lung, the contribution of mesenchymal stem cells to lung regeneration, and advances in bioengineering of lung tissue.

Stem Cell Therapy of Osteoarthritis Using Stromal Vascular Fraction Cells

PUBLISHED in The Journal of Cell Therapy, 2013.   AUTHORS J. Michalek, Z. Kristkova, J. Skopalik, Z. Dudasova, A. Darinskas, R. Moster

Therapy of osteoarthritis relies on non-steroid analgesics, chondroprotectives and in late stages total joint replacement is considered a standard of care. We performed a pilot study using novel stem cell therapy approach that was performed during one surgical procedure. It relies on abdominal lipoaspiration and processing of connective tissue to stromal vascular fraction (SVF) cells that typically contain relatively large amounts of mesenchymal stromal and stem cells. SVF cells are injected immediately to the target joint or to the connective tissue of the target joint.

Stem Cell Orthopedic Specialists Find New Stem Cell Therapies Can Treat Chronic Conditions

PUBLISHED on PRWeb, 2013.

Orthopedic surgery specialists highlight relief from arthritis through stem cells.


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