Research

PROPERTIES OF THE STEM CELL AMNIOTIC FLUID & MEMBRANE

CELLULAR CONTENT, GROWTH FACTORS, AND NUTRITIVE PROPERTIES


Amniotic Fluid and Placental Stem Cells

Delo DM, De Coppi P, Bartsch Jr. G, Atala A. (2006) Methods in Enzymology, 419:426-438. doi:10.1016/S0076-6879(06)19017-5.

Findings:

"The progenitor cells derived from amniotic fluid and placenta are pluripotent and have been shown to differentiate into osteogenic, adipogenic, myogenic, neurogenic, endothelial, and hepatic phenotypes in vitro. Each differentiation has been performed through proof of phenotypic and biochemical changes consistent with the differentiated tissue type of interest.”

Growth Factor mRNA and Protein in Preserved Human Amniotic Membrane.

Koizumi NJ and et al. (2000) Current Eye Research, 20(3):173-7.

Findings:

RT-PCR revealed that human AM expresses mRNA for EGF, TGF-alpha, KGF, HGF, bFGF, TGF-beta1, -beta2, -beta3, KGFR and HGFR…AM without amniotic epithelium also contains all seven growth factors examined, however, in this tissue the protein levels of EGF, KGF, HGF and bFGF were found to be significantly lower than in native AM.

Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine

Rennie K and et al. (2012) Stem Cells International, 2012:721538. doi:10.1155/2012/721538.

Findings:

“Amniotic fluid contains electrolytes, growth factors, carbohydrates, lipids, proteins, amino acids, lactate, pyruvate, enzymes, and hormones…the presence of key growth factors such as EGF, FGF, TGF, HGF in amniotic membranes may account for their clinical effects and mechanisms of action.”

Collagen Types in Normal and Prematurely Ruptured Amniotic Membranes

Kanayama N, Terao T, Kawashima Y, Horiuchi K, and Fujimoto D. (1995) American Journal of Obstetrics and Gynecology, 153(8):899-903.

Findings:

“Collagen types were studied through sodium dodecyl sulfate-polyacrylamide gel electrophoresis in human amnions from pregnant women with or without premature rupture of the membranes. Collagen types I, III, and V were recognized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in all samples.”

Differential Distribution of Subchains of the Basement Membrane Components Type lV Collagen and Laminin Among the Amniotic Membrane, Cornea, and Conjunctiva

Fukuda K, Chikama T, Nakamura M, and Nishida T. (1999) Cornea, 18(1):73-9.

Findings:

“In the conjunctival basement membrane and the amniotic membrane, fluorescence was evident for collagen alpha2(IV)… Laminin-1, laminin-5, fibronectin, and type VII collagen were present in all the basement membranes examined.”


GROWTH FACTORS IN TENDON HEALING


The Roles of Growth Factors in Tendon and Ligament Healing

Molloy T, Wang Y, and Murrel AC. (2003) Sports Med, 33 (5): 381-394.

Findings:

“In vitro and in vivo studies have shown that bFGF is both a powerful stimulator of angiogenesis and a regulator of cellular migration and proliferation. Studies into the effects of the exogenous application of TGF?, IGF-I, PDGF and bFGF into the wound site singly and in combination have shown promise, significantly decreasing a number of parameters used to define the functional deficit of a healing tendon. Application of IGF-I has been shown to increase in the Achilles Functional Index and the breaking energy of injured rat tendon. TGF? and PDGF have been shown separately to increase the breaking energy of healing tendon. Finally, application of bFGF has been shown to promote cellular proliferation and collagen synthesis in vivo.”

Rotator Cuff Disorders: Basic Science and Clinical Medicine

Maffulli N, Furia JP. (2011) JP Medical Series. JP Medical Ltd., 38. ISBN: 1907816089

Findings:

“Numerous growth factors are involved in tendon repair. These include BMPs, EGF, EGF2, IGF-1, IGF-II, PDGF-AA, PDGF-BB, PDGF-AB, and TGF-B…Exogenous supplementation of these factors in failed healing responses, such as resistant tendinopathies may lead to d definitive healing response.”

Biologic Augmentation of Rotator Cuff Tendon-Healing with Use of a Mixture of Osteoinductive Growth Factors

Rodeo, AS. Potter HG, and Atkinson BL. (2007) Journal of Bone and Joint Surgery, 89:2485:97. DOI:10.2106/JBJS.C.01627

Findings:

“In conclusion, we found that a mixture of osteoinductive growth factors leads to increased formation of new bone and soft tissue in a tendon-bone gap, resulting in a stronger attachment between the tendon and bone at six and twelve weeks after repair. We also found improved stiffness of the repairs treated with a collagen scaffold alone. Because clinical studies of rotator cuff repair have demonstrated a relatively high prevalence of failure of complete healing of rotator cuff repairs, the use of extracellular matrix scaffolds and growth factors to augment healing may provide a clinically important improvemen in rotator cuff repair.”

Biologics for Tendon Repair

Docheva D, Muller SA, Majewski M, Evans CH. (2015) Advanced Drug Delivery Reviews, 84:222-239. doi: 10.1016/j.addr.2014.11.015.

Findings:

“Possibly the up-regulation of collagen type III and the down-regulation of collagen type I by cells in the endotenon marks the beginning of tendon healing induced by TGF?… Combined treatment with bFGF and PDGF increases fibronectin deposition as part of the provisional matrix and angiogenesis/revascularization in canine flexor tenocytes. Moreover PDGF stimulates the synthesis of proteoglycan, collagen, non-collagenous protein and DNA; bFGF was shown to accelerate intratendinous healing in patellar tendons. Also IGF-1 stimulates matrix synthesis and cell proliferation of tenocytes in vitro…Combinations of growth factors seem more potent than individual growth factors delivered singly.”

Properties of the Amniotic Membrane for Potential Use in Tissue Engineering

Niknejad H, and et al. (2008) European Cells and Materials, 15:88-99. Findings:

Findings:

“AM scaffold can modulate the healing of a wound by promoting tissue reconstruction rather than promoting scar tissue formation…The AM stromal matrix markedly suppresses the expression of the potent pro-inflammatory cytokines, IL-1? and IL-1?…In addition, 2 low-molecular-mass elastase inhibitors, secretory leukocyte proteinase inhibitor (SLPI) and elafin, are expressed in the AM (King et al., 2007; Buhimschi et al., 2004). In addition to their anti-inflammatory properties, elafin and SLPI both have antimicrobial actions and act as components of the innate immune system to protect related surfaces from infection.”


ANTI-INFLAMMATORY AND ANTI-FIBROTIC


Soluble Factors of Amnion-derived Cells in Treatment of Inflammatory and Fibrotic Pathologies

Silini A, Parolini O, Huppertz B and Lang I. (2013) Current Stem Cell Research and Therapy, 8:6-14. DOI: 10.2174/1574888X113080100003.

Findings:

“The amnion contains various tissue inhibitors (TIMP-1, -2, -3, -4) and MMPs. They regulate many crucial processes in inflammation and fibrotic processes including chemotactic migration of inflammatory cells, mitosis of fibroblasts and synthesis and degradation of extracellular components. This can explain, at least in part, the anti-inflammatory and anti-fibrotic action of the amnion.”

Human Amnion-derived Stem Cells Have Immunosuppressive Properties on NK Cells and Monocytes

Li J, and et al. (2014) Cell Transplantation, DOI: http://dx.doi.org/10.3727/096368914X685230.

Findings:

“In our study, amnion-derived cells exerted an inhibitory effect on NK cell and monocyte activation and function. These data showed that amnion-derived cells have immunosuppressive activity and that IL-10 and PGE2 may be involved in the immunosuppressive activity of amnion-derived cells.”

ANTI-MICROBIAL


Natural Anti-microbial Production by the Amnion

Stock SJ, Kelly RW, Riley SC, Calder AA. (2007) American Journal of Obstetrics and Gynecology, 196(3):e1-255.e6, ISSN 0002-9378. doi:10.1016/j.ajog.2006.10.908.

Findings:

“Natural antimicrobial proteins are ex-pressed throughout the nonpregnant female reproductive tract. In pregnancy, natural antimicrobials are found in the amniotic fluid and have been localized in the placenta, decidua, and fetal membranes.”

Antibacterial Properties of Human Amnion and Chorion in Vitro

Kiaergaard N, and et al. (2001) European Journal of Obstetrics, Gynecology and Reproductive Biology, 94(2):224-9.

Findings:

“An inhibitory effect of fetal membranes against a range of bacteria was found. Consistent results were obtained in experiments with cultures on agar and cultures suspended in agar (membranes from eight women in both studies). In experiments with liquid cultures (seven women) only chorion showed a marginal inhibitory effect. All strains were inhibited, but the most pronounced inhibition was obtained for streptococcus group A, S. aureus and S. saprophyticus by both chorion and amnion.”

Amniotic Fluid: Not Just Fetal Urine Anymore

Underwood MA, Gilbert WM, Sherman MP. (2005) Journal of Perinatology, 25:341-348. doi:10.1038/sj.jp.7211290.

Findings:

“Many of the substances that comprise the innate immune system have been identi?ed in AF and vernix and have been shown to have signi?cant antimicrobial properties; these include the a-defensins [HNP1-3], lactoferrin, lysozyme, bactericidal/permeability-increasing protein, calprotectin, secretory leukocyte protease inhibitor, psoriasin [S100A7], and a-cathelicidin [LL-37].25–27 These potent antimicrobials show broad-spectrum activity against bacteria, fungi, protozoa, and viruses.”


IMMUNOPRIVILEGED AND CHORION-FREE


Amniotic Membrane-derived Stem Cells: Immunomodulatory Properties and Potential Clinical Application

Insausti CL, Blanquer M, Garcia-Hernandez AM, Castellanos G, Moraleda JM. (2014) Stem Cells and Cloning: Advances and Applications, 2014:753-63.

Findings:

“One of the unique characteristics of HAECs and HAMSCs is that they constitutively express the tissue-restricted, nonclassical human leukocyte antigen G (HLA-G). Under physiological conditions, constitutive HLA-G expression is found in immune-privileged organs (eg, testis, ovary, and fetal cells) and is associated with tolerogenic properties via the interaction with inhibitory receptors. HLA-G has been shown to have important immunomodulatory functions.”

Immunogenicity of Human Amniotic Epithelial Cells After Transplantation into Volunteers

Akle CA, Adinolfi M, Welsh KI. (1981) Lancet 2:1003–1005.

Findings:

“None of the volunteers showed clinical signs of acute rejection, and amniotic epithelial cells were demonstrated by biopsy up to 7 weeks after implantation. HLA antibodies were not detected in samples of serum from four volunteers thoroughly investigated…The results suggest that acute immune rejection does not occur after the transplantation of human amniotic epithelial cells.”

Amnion-derived Multipotent Progenitor Cells Support Allograft Tolerance Induction

Anam L and et al. (2013) American Journal of Transplantation, 13:1416-1428. DOI: 10.1002/ajt.12252.

Findings:

“Based on these findings AMPs may, therefore, be a pro-tolerogenic cellular therapeutic that could have clinical efficacy for both solid organ and hematopoietic stem cell transplant applications…Consequently, AMPs may exert their immunosuppressive function directly through release of regulatory mediators and/or ampli?ed regulatory signaling.”

Comparison of Angiogenic, Cytoprotective, and Immunosuppressive Properties of Human Amnion and Chorion-derived Mesenchymal Stem Cells

Yamahara K, and et al. (2014) PLoS One, 9(2):e88319. doi: 10.1371/journal.pone.0088319.

Findings:

“In addition, compared to human chorion MSCs, human amnion MSCs markedly reduced T-lymphocyte proliferation with the enhanced secretion of PGE2, and improved the pathological situation of a mouse model of acute graft-versus-host disease.”

CRYOPRESERVATION


Comparison of Cryopreserved Amniotic Membrane and Umbilical Cord Tissue with Dehydrated Amniotic Membrane/chorion Tissue

Cooke M, and et al. (2014) Journal of Wound Care, 10:465-474, 476. DOI: 10.12968/jowc.2014.23.10.465.

Findings:

“Cryopreservation retains the native architecture of the AM/UC extracellular matrix and maintains the quantity and activity of key biological signals present in fresh AM/UC, including high molecular weight hyaluronic acid, heavy chain-HA complex, and pentraxin 3. In contrast, dehydrated tissues were structurally compromised and almost completely lacked these crucial components.”


CLINICAL APPLICATIONS OF AMNIOTIC FLUID & MEMBRANE

ORTHOPEDICS/BONE REPAIR


Nonsurgical Resolution of Distal Fibula Fracture with FloGraft® Implant; 82 YO Male

Jacoby, Richard (2014)

Findings:

“Previous clinical observations demonstrated that Fl Graft® has been highly effective in resolving various bone fractures with minimal invasiveness; patients have been able to return to a better quality of life than with standard of care… Thus, incorporating Fl Graft® as an integral part of the treatment process is important to achieving a curative outcome in patients with advanced age, rather than relying solely on standard palliative care. Fl Graft® represents a much needed bridge between palliative care and surgical intervention.”

The Use of Amniotic Fluid Concentrate in Orthopedic Conditions

Shimberg M. (1938) The Journal of Bone and Joint Surgery, XX(1):167-77.

Findings:

“Clinically it [amniotic fluid concentrate] was observed in these twenty-six cases that postoperative pain was reduced to a minimum. As compared with cases in which the concentrate was not used, this difference was striking… No postoperative adhesions occurred in any case. In all twenty-six cases the final functional result could be fairly rated as “good” to “excellent”. It was found that function was more easily and rapidly restored when the concentrate was employed… The results obtained by arthrotomy after injection of this fluid in this study compare favorably with those of others as regards [to] postoperative complications, time of functional restoration, and final end results. In fractures of the intra-articular type, there is no doubt that the fluid has definite value. In atrophic arthritis, it seems indicated where there is effusion or marked synovial-membrane involvement.”

Evaluation of Amniotic-Derived Membrane Biomaterial as an Adjunct for Repair of Critical Sized Bone Defects

Starecki M, Schwartz JA, and Grande DA. (2014) Advances in Orthopedic Surgery, DOI: http://dx.doi.org/10.1155/2014/572586.

Findings:

“The study demonstrates that amniotic membrane products have potential to provide bridging of bone defects. Filling bone defects without harvesting autogenous bone would provide a significant improvement in patient care.”

Effect of Human Amniotic Fluid on Bone Healing

Karacal N, Kosucu P, Cobanglu U and Kutlu N. (2005) Journal of Surgical Research, 129(2):283-7.

Findings:

“The defects from group 1, which were treated with human amniotic fluid, showed significantly higher ossification than the group 2 defects, which were instilled with saline solution. Histological examination at 6 weeks postoperatively revealed that the defects treated with human amniotic fluid (group 1) had superior ossification compared with the control group defects (group 2).”

Exploring the Application of Mesenchymal Stem Cells in Bone Repair and Regeneration

Griffin M, Iqbal SA and Bayat A. (2011) Journal of Bone Joint Surgery [British], 93-B: 427-34.

Findings:

“It is clear from the various studies discussed above that the application of MSCs to bone defects enhances bone formation without any adverse reactions to the patients.”


TENDONS/LIGAMENTS


Use of FloGraft® in Achilles Tendonopathy and Enthesopathy

Willams, Marie (2013)

Findings:

“In conclusion, FloGraft® is a powerful biological allograft, derived from human amnion and amniotic fluid, which is a potent anti-inflammatory, anti-adhesive, anti-infective fluid, which increases healing by sending a signal to recruit healthy cells to migrate to unhealthy damaged tissue and promotes rapid healing within the tissues. When applied to the treatment of enthesopathy of the Achilles tendon, it is an excellent alternative to surgical repair of the thickened, fibrotic Achilles tendon and is effective in eliminating the resultant recalcitrant heel pain.”

Achilles Tendonosis Case Series

Bregman P and Jacoby R. (2014)

Findings:

“In another retrospective study of over 30 patients, we found a success rate of 87% with Fl?Graft (without laser therapy) in patients who had previously failed all conservative treatment and would have moved toward surgical intervention. Success was defined as the patient being pain-free and able to return to pre-injury function.”

Synovial Mesenchymal Stem Cells Accelerate Early Remodeling of Tendon-bone Healing

Ju YJ, Muneta T, Yoshimura H, Koga H, Sekiya I. (2008) Cell Tissue Research, 332:469-478. DOI 10.1007/s00441-008-0610-z.

Findings:

"In conclusion, implanted synovial MSCs improve early remodeling of the tendon-bone healing at 1 and 2 weeks histologically….If the treatment of MSCs produces a clinical effect, even in only the early phase after ligament surgery, it could improve rehabilitation and produce a better outcome for ligament reconstruction.”

Anterior Cruciate Ligament Regeneration Using Mesenchymal Stem Cells and Collagen Type I Scaffold in a Rabbit Model

Figueroa D, and et al. (2014) Knee Surgery, Sports Traumatology, Arthroscopy, 22(5):1196-202. doi: 10.1007/s00167-013-2471-6.

Findings:

“…the use of MSC seeded in a collagen type I scaffold in the treatment of ACL injuries is associated with an enhancement of ligament regeneration. This MSC-based technique is a potentially attractive tool for improving the treatment of ACL ruptures.”

Indirect Co-Culture with Tendons or Tenocytes Can Program Amniotic Epithelial Cells towards Stepwise Tenogenic Differentiation

Barboni B, and et al. (2012) PLoS One, 7(2): e30974.

Findings:

“The morphological and functional analysis indicated that AEC possessed tenogenic differentiation potential. However, only AEC exposed to fetal-derived cell/tissues developed in vitro tendon-like three dimensional structures with an expression profile of matrix (COL1 and THSB4) and mesenchymal/tendon related genes (TNM, OCN and SCXB) similar to that recorded in native ovine tendons. The tendon-like structures displayed high levels of organization as documented by the cell morphology, the newly deposited matrix enriched in COL1 and widespread expression of gap junction proteins (Connexin 32 and 43).”

Amnion-Derived Multipotent Progenitor Cells Improve Achilles Tendon Repair in Rats

Philip J, and et al. (2013) Eplasty, 13: e31. PMCID: PMC3690753.

Findings:

“Amnion-derived multipotent progenitor cells have a positive effect on healing tendons by improving mechanical strength and elastic modulus during the healing process. The presented findings suggest the clinical utility of AMP cells in facilitating the healing of ruptured tendons. Both the Young modulus and yield strengths of tendons increased significantly following treatment with AMP cells.”

Investigating the Efficacy of Amnion-derived Compared with Bone-marrow Derived Mesenchymal Stromal Cells in Equine Tendon and Ligament Injuries

Lange-Consiglio, A and et al. (2013) Cytotherapy, 15(8):1011-20. DOI: 10.1016/j.jcyt.2013.03.002.

Findings:

“The possibility to inject allogeneic AMSCs in real time, before any ultrasonographic change occurs within the injured tendon and ligament, together with the higher plasticity and proliferative capacity of these cells compared with BM-MSCs, represents the main features of interest for this novel approach for the treatment of equine tendon diseases. An obvious active proliferative healing in the area injected with AMSCs makes these cells more effective than BM-MSCs.”

Achilles tendon regeneration can be improved by amniotic epithelial cell allotransplantation

Barboni B and et al. (2012) Cell Transplantation, 21:2377–2395.

Findings:

“In conclusion, the present study demonstrates that AECs can accelerate and positively modulate the process of tendon healing by stimulating a prompt recovery of microarchitecture and biomechanical properties of experimentally injured tendons. AECs, in fact, improved tendon repair and influenced the production of biomolecules crucial for tendon regeneration (VEGF, TGF-b1), modulating local inflammatory reaction, and blood vessel network remodeling. AECs stimulated the process of healing conjugating a strong paracrine role with a direct contribution in the synthesis of new tendon matrix. Altogether, these results encourage the use of AECs as a new cell source that did not require any preliminary in vitro differentiation or genomic transfection.”

SPINAL CORD INJURY


Current and Future Applications for Stem Cell Therapies in Spine Surgery

Goldschlager T, and et al. (2013) Current Stem Cell Research & Therapy, 8(5):381-393.

Findings:

“...studies have shown that some cells, particularly mesenchymal stromal cells, modulate oxidative stress and secrete cytokines and growth factors that have immunomodulatory, antiinflammatory, angiogenic and antiapoptotic effects. It is these combined characteristics that make cell based therapies prime candidates for advancing current techniques in spine surgery and for providing new strategies directed at targeting the underlying causes of spinal diseases and disorders to promote repair and regeneration.”

Concise Review: Isolation and Characterization of Cells from Human Term Placenta: Outcome of the First International Workshop on Placenta Derived Stem Cell

Parolini O and et al. (2008) Stem Cells, 26:300-311.

Findings:

“In conclusion, hAEC transplants produce beneficial results in animal models of spinal cord injury. They were found to exhibit neuroprotection in acute phases of injury and facilitate regeneration of long tracts in long-term phases of recovery, as measured by behavioral assessment. The beneficial effects may be mediated through the secretion of novel neurotrophic factors.”

Third trimester NG2-positive amniotic fluid cells are effective in improving repair in spinal cord injury

Bottai D, and et al. (2014) Experimental Neurology, 254:121-133.

Findings:

“This study shows that the transplantation of a specific subclass of AFCs [amniotic fluid cells] is capable of promoting motor functional recovery after spinal cord injury in the mouse…the effectiveness of the transplanted AFCs appears not mediated by the substitution of the lost neural tissue, but rather by attenuation of myelin loss and reduction of inflammatory cell influx into the lesion site.”

Role of human amniotic epithelial cell transplantation in spinal cord injury repair research

Sankar V, Muthusamy R. (2003) Neuroscience, 118(1):11-17.

Findings:

“The present study reveals that HAEC may exert beneficial effects such as neurotrophism and/or rescuing axotomized neurons when transplanted into the injured spinal cord…HAEC outweigh neural tissue grafts by several factors given below. First, HAEC survived well even in the totally transected spinal cord whereas under similar conditions, neural cells showed poor survival (unpublished personal observations)…Second, HAEC did not evoke an immune response due to their non-antigenic nature…Third, in neural tissue grafts, no glial fiber formation was reported whereas in the present study, glial fibers were seen developing within the HAEC grafts. This may be taken as an advantageous feature since formation of “glial channels” in an area before axonal arrival was considered as an important axon guiding mechanism.”

FOOT AND ANKLE


Use of FloGraft® in Ankle Cartilage Repair via Ankle Arthroscopy

Bernstein, Stephen A (2014)

Findings:

“In conclusion, FloGraft® is a significant adjunct to any arthroscopic surgery of the Foot and Ankle….FloGraft® tissue promoted earlier than expected articular cartilage healing in this patient.”

Safety Analysis of Cryopreserved Amniotic Membrane/umbilical Cord Tissue in Foot and Ankle Surgery: a Consecutive Case Series of 124 Patients

DeMill SL, Granata JD, McAlister JE, Berlet GC, Hyer CF. (2014) Surgical Technology International. 25:257:261.

Findings:

“The results of this study demonstrate that the use of amnion tissue in the foot and ankle setting is safe with a decreasing trend in overall complication rates compared with historically published norms.”

Human Amniotic Allograft in Use on Talar Dome Lesions: A Prospective Report of 37 Patients

Anderson JJ, Swayzee Z, Hansen MH. (2014) Stem Cell Discovery, 4, 55-60

Findings:

“The addition of HAA to arthroscopic micro-fracture repair of talar dome lesions measuring less than 2 cm2 has shown to significantly improve both post-operative VAS scores, when compared to preoperative scores. This improvement in ACFAS and VAS scores speaks to the potential use of HAA in the treatment of OCD…While the use of HAA has not been delineated as far as the techniques and applications in the ankle joint, it is accepted and has shown to be an effective allograft and a naïve tissue in which its potential to differentiate can assists in healing. Possibly as an adjunct to further intervention, it is felt that this will allow hyaline cartilage development and the potential to develop into a more significant structural cartilage.”

Amniotic Tissues for the Treatment of Chronic Plantar Fasciitis and Achilles Tendinosis


DEGENERATIVE JOINTS/CARTILAGE


Potential Use of the Human Amniotic Membrane as a Scaffold in Human Articular Cartilage Repair

Diaz-Prado S, and et al. (2010) Cell Tissue Banking, 11(2):183-95. doi: 10.1007/s10561-009-9144-1.

Findings:

“In vitro repair experiments showed formation on OA cartilage of new tissue expressing type II collagen. Integration of the new tissue with OA cartilage was excellent. The results indicate that cryopreserved HAMs can be used to support chondrocyte proliferation for transplantation therapy to repair OA cartilage.”

Technology Insight: Adult Mesenchymal Stem Cells for Osteoarthritis Therapy

Noth U, Steinert AF, and Tuan RS. (2008) Nature: Clinical Practice Rheumatology, 4(7):371-380. doi:10.1038/ncprheum0816

Findings:

“Joints exposed to MSCs showed evidence of marked regeneration of the medial meniscus, and implanted cells were detected in the newly formed tissue. Articular cartilage degeneration, osteophytic remodeling, and subchondral sclerosis were also reduced in the treated joints… In the long term, we hope that MSC-based technologies will permit the engineering of cartilage not only for repair of focal lesions but also as a treatment option for OA joints, to realize the ultimate goal of a fully biological prosthesis.”

Mesenchymal Stem Cells in Arthritic Diseases

Chen FH, Tuan RS. (2008) Arthritis Research & Therapy, 10:223. doi:10.1186/ar2514.

Findings:

"Recent advances in our understanding of the functions of MSCs have shown that MSCs also possess potent immunosuppression and anti-inflammation effects. In addition, through secretion of various soluble factors, MSCs can influence the local tissue environment and exert protective effects with an end result of effectively stimulating regeneration in situ. This function of MSCs can be exploited for their therapeutic application in degenerative joint diseases such as RA and OA…MSCs offer great hope in relieving the disease burden of degenerative joint diseases through their application in the form of replacement tissue as well as local or systemic cell therapy.”


WOUND HEALING


Use of Amniotic Membrane Transplantation in the Treatment of Venous Leg Ulcers

Mermet I, and et al. (2007) Wound Rep Reg, 15:459-464. DOI:10.1111/j.1524-475X.2007.00252.x.

Findings:

“All patients experienced a significant reduction of ulcer-related pain rapidly after AM transplantation. No adverse events were recorded. AM transplantation seems to function as a safe substrate, promoting proper epithelialization while suppressing excessive fibrosis. Further advantages of biotherapy with AM are its easy and low-cost production, and that it can be applied as an ambulatory treatment without immobilization. AM transplantation may thus be considered to be an alternative method for treating chronic leg ulcers.”

FloGraft® Rapidly Moves Stalled Wounds into the Proliferative Phase

Gottlieb, Marc (2014)

Findings:

“Twenty-six patients of the pilot study (96%; N=27) demonstrated rapid acceleration toward margin closure within twenty-one (21) days from initial AmnioGenic Therapy® treatment. Therefore, the preliminary results suggest that cryopreserved, amnion-derived, flowable allograft, e.g. Fl?Graft®, represents an effective chronic wound management treatment option that merits a randomized controlled trial.”

The Use of Amniotic Fluid and Membrane* in Treatment of Chronic Lower Extremity Ulcerations and Achilles Tendon Injuries

Frykberg RG (DPM, MPH), Banks J (DPM), Spicer J (DPM), Wilke L (DPM), Tierney EW (DPM), Tallis AJ (DPM) (2014) Poster Presentation, Phoenix VA Healthcare System.

Findings:

“The results show promising results for the use of amniotic fluid and membrane* in the treatment of refractory wounds and Achilles tendon injuries.”

Wound Closure and Limb Salvage Following Total Knee Arthroplasty Using Amniotic Fluid and Amniotic Membrane

Swartz G, and Kozak I. Poster Presentation, Phoenix VA Healthcare System.

Findings:

“The use of amniotic fluid and amniotic membrane can be another method of closing a chronically draining knee wound that was not successfully closed by conventional methods.”

Human Amnion as an Adjunct in Wound Healing

Falk WP, Matthews R, Stevens PJ, Bennett JP, et al. (1980) The Lancet 1(8179):1156-8. DOI: 10.1016/S0140-6736(80)91617-7.

Findings:

“After amnion application there was considerable granulation tissue in the ulcer bed and microscopical evidence of thinned connective tissues, vessel development, more compact resolution of vascular basement membranes, and many more factor VIII granules within endothelial cells. These findings suggest the presence of angiogenic factors in human amnion and this could explain the hitherto unexplained success of amniotic membranes in surgical practice.”

Hyaluronic Acid, an Important Factor in the Wound Healing Properties of Amniotic Fluid: In Vitro Studies of Re-epithelialisation in Human Skin Wounds.

Nyman E, Huss, F, Nyman T, Junker J, and Kratz G. (2013) Journal of Plastic Surgery and Hand Surgery, 47(2):89-92. doi: 10.3109/2000656X.2012.733169.

Findings:

“In conclusion, amniotic fluid promotes accelerated re-epithelialisation and hyaluronic acid is an important ingredient.”

ADHESION BARRIER


Implantation of Amniotic Membrane to Reduce Postlaminectomy Epidural Adhesions

Huiren T and Hongbin F. (2009) Eur Spine J, 18(8):1202-1212. doi:10.1007/s00586-009-1013-x.

Findings:

“In conclusion, this study suggests that CAM is an effective anti-scar adhesion material, which can decrease adhesion tenacity and scar amount in epidural space. The findings also indicate the potentials of applying CAM in humans to minimize postoperative complications.”

Regeneration of Peritoneum Using Amniotic Membrane to Prevent Postoperative Adhesions

Kuriu Y, and et al. (2009) Hepatogastroenterology, 56(93):1064-8.

Findings:

“Amniotic membrane grafts reduced intraperitoneal adhesions after surgical trauma, were well absorbed, and served as a substrate for regenerating mesothelium.”

Effects of Human Amniotic Fluid on Peritendinous Adhesion Formation and Tendon Healing after Flexor Tendon Surgery in Rabbits

Ozgenel GY, Samli B and Ozcan M. (2001) Journal of Hand Surgery, 26(2):332-9.

Findings:

“The least adhesion and the best healing were observed in tendons treated with sheath repair and HAF application. Tendons treated with HAF had significantly higher tensile load values. Topical application of HAF immediately after tenorrhaphy is significantly effective in preventing peritendinous adhesion formation without impairment of tendon healing in this rabbit model.”


NERVE


Addressing Morton’s Nerve Entrapment Surgically and Non-surgically with Fl?Graft®

Peter (2014)

Findings:

“In a retrospective cohort of 15 patients, 14 of 15 (93%) patients with Morton’s Nerve Entrapment were resolved using Fl?Graft® during the conservative treatment plan. In 15 patients that did not receive Fl?Graft® during the conservative treatment plan, 3 of 15 (20%) patients were resolved and the remaining 12 patients (80%) went on to require surgical intervention. In patients that required surgical intervention (n=27), there was a 95% success rate when Fl?Graft® was incorporated during the decompression surgery. Patients reported reduced pain and quicker healing of the incision line when Fl?Graft® was used during the surgical decompression.”

Tarsal Tunnel Compression Neuropathy Case Study Using Fl?Graft®

Jacoby, Richard (2014)

Findings:

“From our retrospective cohort of five patients, we have observed 100% success rate in restoring nerve function via Dellon decompression and Fl?Graft®. The average time to full functionality has been 5.5 weeks.”

Extracellular Matrix of Human Amnion Manufactured into Tubes as Conduits for Peripheral Nerve Regeneration

Mligiliche N and et al. (2002) Journal of Biomedical Materials Research, 63(5):591-600. DOI: 10.1002/jbm.10349.

Findings:

“Reinnervation to the gastrocnemius muscle was demonstrated electrophysiologically 9 months after implantation…Therefore, it can be said that the AMTs tubes are biodegradable but persist for a long duration to support the regenerating nerve fibers…It was concluded that the extracellular matrix sheet from the human amnion is an effective conduit material for peripheral nerve regeneration.”

Amniotic Mesenchymal Stem Cells Display Neurovascular Tropism and Aid in the Recovery of Injured Peripheral Nerves

Li Y, Guo L, Ahn HS, Kim MH, Kim S. (2014) J. Cell. Mol. Med., 18(6): 1028-1034.

Findings:

“First, the local transplantation of AMMs restored the NCVs of nerves. Second, AMM injection induced the revascularization of nerves. Third, the injected AMMs highly engrafted in the sciatic nerve and incorporated with the vasa nervorum. Fourth, the expression of angiogenic factors in the nerves was increased by AMM implantation…. In conclusion, we demonstrated that AMM transplantation improved the functional outcome in sciatic nerve injury.”

PAIN MANAGEMENT


Regenerative Medicine in Pain Management

McJunkin T, Lynch P, Deer TR, Anderson J and Desai R. (2012) Pain Medicine News Special Edition. McMahon Publishing.

Findings:

“The application of human amniotic membranes within the field of interventional pain management is currently a topic of great interest. Much of the current research is investigating its role in the treatment of tissue damage and inflammation, such as tendonosis and tendonitis…..Additional research in the field of human amniotic membrane applications in interventional pain management is needed, but animal model research studies and anecdotal reports of its use in human subjects are promising.”

Update on Amniotic Membrane Transplantation

Liu J, and et al. (2010) Expert Rev Ophthalmology, 5(5): 645–661. doi:10.1586/eop.10.63.

Findings:

“Although one may attribute AM’s effect in relieving pain to its anti-inflammatory action, we suspect that such a rapid action in pain relief may be mediated by an as-yet unknown antipain action that deserves further investigation.”

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