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1.
J Vasc Surg ; 52(3): 723-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20576396

ABSTRACT

BACKGROUND: Unreconstructable critical ischemia with gangrene of the upper extremity is rarely due to atherosclerosis alone, and few treatment options exist. We describe a patient with gangrene of both hands as a result of unreconstructable atherosclerotic disease of both upper extremities who was successfully treated with tissue repair cells (TRCs) produced from the patient's bone marrow. METHODS: A patient with type 1 diabetes was referred with bilateral upper extremity digital gangrene due to unreconstructable forearm and hand atherosclerosis. He was evaluated for therapeutic angiogenesis using TRCs. RESULTS: Following the intramuscular injection of TRCs produced from autologous bone marrow stem cells, the patient demonstrated improved arterial perfusion and a durable clinical response with healing of all amputation sites and cessation of pain. CONCLUSIONS: The production of TRCs results in the expansion of stem and early progenitor cells, including CD90+ mesenchymal cells and endothelial progenitor cells. This is the first reported case of end-stage upper extremity ischemia treated with TRCs harvested from adult bone marrow.


Subject(s)
Adult Stem Cells/transplantation , Bone Marrow Transplantation , Ischemia/surgery , Neovascularization, Physiologic , Upper Extremity/blood supply , Wound Healing , Amputation, Surgical , Angiography, Digital Subtraction , Gangrene , Humans , Ischemia/diagnosis , Ischemia/pathology , Ischemia/physiopathology , Laser-Doppler Flowmetry , Male , Middle Aged , Photoplethysmography , Recovery of Function , Transplantation, Autologous , Treatment Outcome
2.
J Bone Miner Res ; 18(4): 624-36, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12674323

ABSTRACT

An 8-month-old girl who seemed certain to die from the infantile form of hypophosphatasia, an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP), underwent the first trial of bone marrow cell transplantation for this heritable type of rickets. After cytoreduction, she was given T-cell-depleted, haplo-identical marrow from her healthy sister. Chimerism in peripheral blood and bone marrow became 100% donor. Three months later, she was clinically improved, with considerable healing of rickets and generalized skeletal remineralization. However, 6 months post-transplantation, worsening skeletal disease recurred, with partial return of host hematopoiesis. At the age of 21 months, without additional chemotherapy or immunosuppressive treatment, she received a boost of donor marrow cells expanded ex vivo to enrich for stromal cells. Significant, prolonged clinical and radiographic improvement followed soon after. Nevertheless, biochemical features of hypophosphatasia have remained unchanged to date. Skeletal biopsy specimens were not performed. Now, at 6 years of age, she is intelligent and ambulatory but remains small. Among several hypotheses for our patient's survival and progress, the most plausible seems to be the transient and long-term engraftment of sufficient numbers of donor marrow mesenchymal cells, forming functional osteoblasts and perhaps chondrocytes, to ameliorate her skeletal disease.


Subject(s)
Bone Marrow Transplantation , Hypophosphatasia/therapy , Alkaline Phosphatase/deficiency , Alkaline Phosphatase/genetics , Base Sequence , Bone and Bones/diagnostic imaging , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Hypophosphatasia/diagnostic imaging , Hypophosphatasia/genetics , Hypophosphatasia/metabolism , Infant , Mutation, Missense , Radiography , Stromal Cells/transplantation
3.
Blood ; 101(12): 5061-7, 2003 Jun 15.
Article in English | MEDLINE | ID: mdl-12595310

ABSTRACT

Allogeneic stem cell transplantation with umbilical cord blood (UCB) cells is limited by the cell dose a single unit provides recipients. Ex vivo expansion is one strategy to increase the number of cells available for transplantation. Aastrom Biosciences developed an automated continuous perfusion culture device for expansion of hematopoietic stem cells (HSCs). Cells are expanded in media supplemented with fetal bovine serum, horse serum, PIXY321, flt-3 ligand, and erythropoietin. We performed a phase 1 trial augmenting conventional UCB transplants with ex vivo-expanded cells. The 28 patients were enrolled on the trial between October 8, 1997 and September 30, 1998. UCB cells were expanded in the device, then administered as a boost to the conventional graft on posttransplantation day 12. While expansion of total cells and colony-forming units (CFUs) occurred in all cases, the magnitude of expansion varied considerably. The median fold increase was 2.4 (range, 1.0-8.5) in nucleated cells, 82 (range, 4.6-266.4) in CFU granulocyte-macrophages, and 0.5 (range, 0.09-2.45) in CD34+ lineage negative (lin-) cells. CD3+ cells did not expand under these conditions. Clinical-scale ex vivo expansion of UCB is feasible, and the administration of ex vivo-expanded cells is well tolerated. Augmentation of UCB transplants with ex vivo-expanded cells did not alter the time to myeloid, erythroid, or platelet engraftment in 21 evaluable patients. Recipients of ex vivo-expanded cells continue to have durable engraftment with a median follow-up of 47 months (range, 41-51 months). A randomized phase 2 study will determine whether augmenting UCB transplants with ex vivo-expanded UCB cells is beneficial.


Subject(s)
Cell Division , Cord Blood Stem Cell Transplantation/methods , Hematopoietic Stem Cells/cytology , Adolescent , Adult , Animals , Cattle , Cells, Cultured , Child , Child, Preschool , Colony-Forming Units Assay , Cord Blood Stem Cell Transplantation/mortality , Culture Media , Disease-Free Survival , Fetal Blood , Graft Survival , Graft vs Host Disease/epidemiology , Graft vs Host Disease/mortality , Humans , Infant , Recurrence , Time Factors , Treatment Outcome
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