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.

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Human Adipose Tissue Is a Source of Multipotent Stem Cells

The clinical manifestations of Fanconi’s anemia, an autosomal recessive disorder, include progressive pancytopenia, a predisposition to neoplasia, and nonhematopoietic developmental anomalies [1-3]. Hypersensitivity to the clastogenic effect of DNA-cross-linking agents such as diepoxybutane acts as a diagnostic indicator of the genotype of Fanconi’s anemia, both prenatally and postnatally [3-6]. Prenatal HLA typing has made it possible to ascertain whether a fetus is HLA-identical to an affected sibling [7]. We report here on hematopoietic reconstitution in a boy with severe Fanconi’s anemia who received cryo-preserved umbilical-cord blood from a sister shown by prenatal testing to be unaffected by the disorder, to have a normal karyotype, and to be HLA-identical to the patient. We used a pretransplantation conditioning procedure developed specifically for the treatment of such patients [8]; this technique makes use of the hypersensitivity of the abnormal cells to alkylating agents that cross-link DNA [9,10] and to irradiation [11] In this case, the availability of cord blood obviated the need for obtaining bone marrow from the infant sibling. This use of cord blood followed the suggestion of one of us that blood retrieved from umbilical cord at delivery, usually discarded, might restore hematopoiesis – a proposal supported by preparatory studies by some of us [12] and consistent with reports on the presence of hematopoietic stem and multipotential (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells in human umbilical-cord blood (see the references cited by Broxmeyer et al. [12]).

Hematopoietic reconstitution in a patient with fanconi's anemia by means of umbilical-cord blood from an hla-identical sibling

Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood.

https://www2.dti.ufv.br/noticia/files/anexos/phpLlyEH4_5654.pdf

Isolation of multipotent mesenchymal stem cells from umbilical cord blood.

Background Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. Methods We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Results Among 78 recipients of cord blood from related donors, the Kaplan–Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-misma...

https://www.nejm.org/doi/pdf/10.1056/NEJM199708073370602

Outcome of cord-blood transplantation from related and unrelated donors

The purpose of this study was to evaluate human umbilical cord blood as an alternative to bone marrow in the provision of transplantable stem/progenitor cells for hematopoietic reconstitution Although no direct quantitative assay for human hematopoietic repopulating cells is at present available, the granulocyte-macrophage progenitor cell (CFU-GM) assay has been used with success as a valid indicator of engrafting capability We examined greater than 100 collections of human umbilical cord blood for their content of nucleated cells and granulocyte-macrophage, erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells, in many cases both before and after cryopreservation First it was determined that granulocyte-macrophage, erythroid, and multipotential progenitor cells remained functionally viable in cord blood untreated except for addition of anticoagulant for at least 3 days at 4 degrees C or 25 degrees C (room temperature), though not at 37 degrees C, implying that these cells could be satisfactorily studied and used or cryopreserved for therapy after transport of cord blood by overnight air freight carriage from a remote obstetrical service Granulocyte-macrophage progenitor cells from cord blood so received responded normally to stimulation by purified recombinant preparations of granulocyte-macrophage, granulocyte, and macrophage colony-stimulating factors and interleukin 3 The salient finding, based on analysis of 101 cord blood collections, is that the numbers of progenitor cells present in the low-density (less than 1077 gm/ml) fraction after Ficoll/Hypaque separation typically fell within the range that has been reported for successful engraftment by bone marrow cells Another observation of practical importance is that procedures to remove erythrocytes or granulocytes prior to freezing, and washing of thawed cells before plating, entailed large losses of progenitor cells, the yield of unwashed progenitor cells from unfractionated cord blood being many times greater The provisional inference is that human umbilical cord blood from a single individual is typically a sufficient source of cells for autologous (syngeneic) and for major histocompatibility complex-matched allogeneic hematopoietic reconstitution

https://www.pnas.org/content/pnas/86/10/3828.full.pdf

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells

It has been shown that major histocompatibility complex (MHC) types affect the mating choices of mice and that mice can be trained to distinguish arms of a Y maze scented by odors from MHC-congeneic mice. It is now shown that sensory discrimination of MHC types by trained mice in the Y maze is equally effective with urine as the source of odors. Trained mice, male and female, successfully distinguished between urines of MHC-dissimilar F2 segregants of an MHC-congeneic cross but not between urines of MHC-identical F2 segregants. In a control study with a transfer of training procedure, in which reward was withheld to eliminate any basis for new learning, the trained mice successfully distinguished between urines from panels of MHC-congeneic inbred and F2 segregant congeneic mice that had not previously been used as urine donors. Thus urine, which is a source of chemosensory signals in many species, is also a potent source of the MHC-determined odors that distinguish individual mice.

https://www.pnas.org/content/pnas/78/9/5817.full.pdf

Distinctive urinary odors governed by the major histocompatibility locus of the mouse.

Genetic polymorphism in the H-2:Qa:Tla region of chromosome 17 is associated with constitutive variation of bodily odor phenotypes which permit individual olfactory recognition among mice. To determine whether known genes in the H-2:Qa:Tla complex are concerned in the constitution of odor phenotypes, mice were tested for their ability to sense a difference between the B6/By (H-2b) and congeneic B6.C-H-2bm1 strains, which differ genetically by mutation of the H-2K gene. As in previous studies of the sensory discrimination of H-2:Qa:Tla phenotypes, mice were trained by reward in a Y maze to distinguish the odors of urine samples, and the successful distinctions of B6/By from B6.C-H-2bm1 were confirmed by transfer of training, without reward, to coded samples of urine from genetically equivalent urine donor mice which the trained mice had not previously encountered. Cosegregation of odor phenotype with H-2b and H-2bm1 was demonstrated by transfer of training to typed H-2b and H-2bm1 homozygous segregants of F2 generations of appropriate crosses. Although it is not excluded that the differences in odor phenotype which distinguish H-2b and H-2bm1 mice are directly related to the structure of the H-2b and H-2bm1 products, it is equally possible that H-2-related odor phenotypes arise from effects of H-2 genetic variation on metabolic pathways either directly, or indirectly through developmental polymorphism.

Sensory distinction between H-2b and H-2bm1 mutant mice.

Altered nucleic acid metabolism in human cell cultures infected with mycoplasma.

It is known that mice can distinguish the H-2 haplotypes of other mice by scent and that urine is a potent source of the characteristic odors governed by H-2. It now is shown that genetic disparity confined to the Qa:Tla region of chromosome 17, adjacent to H-2, is accompanied by distinctive urinary scents that can be distinguished by trained mice in a Y maze. This was confirmed by the transfer of training procedure in which mice trained to distinguish the urine of B6 mice from the urine of recombinant congeneic B6-Tlaa mice successfully distinguished the urines of Tlaa and Tlab homozygous F2 segregants of the cross B6 X B6-Tlaa in the absence of reward, including blind trials with coded urine samples. It also is shown that genetic disparity confined to the K end of H-2 is accompanied by distinctive urinary scents recognized in the Y maze. Thus, mice trained to distinguish the urines of B10 from B10.A congeneic mice successfully distinguished various combinations of B10, B10.A, and B10.A (2R, 3R, 5R, and 18R) recombinant congeneic mice representing genetic differences limited to the K end of H-2. It is suggested that the individual scents of mice comprise several odorous components, at least some of which may be incidental to quantitative or qualitative metabolic variations arising from polymorphism of genes such as H-2.

https://www.pnas.org/content/pnas/79/24/7828.full.pdf

Lewis Thomas

Papers

Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells

Distinctive urinary odors governed by the major histocompatibility locus of the mouse.

Sensory distinction between H-2b and H-2bm1 mutant mice.

Altered nucleic acid metabolism in human cell cultures infected with mycoplasma.

Chemosensory recognition of phenotypes determined by the Tla and H-2K regions of chromosome 17 of the mouse